Journal articles: 'Anti-idiotype'

1

Tzioufas, Athanasios G., and John G. Routsias. "Idiotype, anti-idiotype network of autoantibodies." Autoimmunity Reviews 9, no. 9 (2010): 631–33. http://dx.doi.org/10.1016/j.autrev.2010.05.013.

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2

McCarthy, Helen, Christian H. Ottensmeier, Terry J. Hamblin, and Freda K. Stevenson. "Anti-idiotype vaccines." British Journal of Haematology 123, no. 5 (2003): 770–81. http://dx.doi.org/10.1046/j.1365-2141.2003.04698.x.

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3

THANAVALA, Y. "Anti-idiotype vaccines." Trends in Biotechnology 7, no. 3 (1989): 62–66. http://dx.doi.org/10.1016/0167-7799(89)90065-6.

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4

Hsu, Kuo‐Hui, and Fun S. Chu. "Anti‐idiotype and anti‐anti‐idiotype antibodies for aflatoxin from laying hens." Food and Agricultural Immunology 7, no. 2 (1995): 163–74. http://dx.doi.org/10.1080/09540109509354875.

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5

Iwasaki, Yoshiaki, Hiroyuki Takabatake, Toshiyuki Shinji, Marc Monestier, and Soldano Ferrone. "Structural profile of idiotype, anti-idiotype and anti-anti-idiotype monoclonal antibodies in the HLA-DQ3 antigenic system." European Journal of Immunology 24, no. 11 (1994): 2874–81. http://dx.doi.org/10.1002/eji.1830241144.

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6

TAUSSIG, M. J., D. KIRK, M. W. WANG, et al. "Idiotype-Anti-Idiotype Interactions of VHIX-Coded Anti-Progesterone and Anti-Arsonate Antibodies." Scandinavian Journal of Immunology 26, no. 3 (1987): 267–76. http://dx.doi.org/10.1111/j.1365-3083.1987.tb02260.x.

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7

Langone, John J., and Robert J. Bjercke. "Idiotype-anti-idiotype hapten immunoassays: Assay for cotinine." Analytical Biochemistry 182, no. 1 (1989): 187–92. http://dx.doi.org/10.1016/0003-2697(89)90740-9.

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8

Tankersley, Donald L., M. Sue Preston, and J. S. Finlayson. "Immunoglobulin G dimer: An idiotype-anti-idiotype complex." Molecular Immunology 25, no. 1 (1988): 41–48. http://dx.doi.org/10.1016/0161-5890(88)90088-0.

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9

Chu, Fun S., Xuan Huang, and Chris M. Maragos. "Production and characterization of anti-idiotype and anti-anti-idiotype antibodies against fumonisin B1." Journal of Agricultural and Food Chemistry 43, no. 1 (1995): 261–67. http://dx.doi.org/10.1021/jf00049a046.

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10

Hsu, Kuo‐Hui, and Fun S. Chu. "Anti‐idiotype and anti‐anti‐idiotype antibodies generated from polyclonal antibodies against aflatoxin b1." Food and Agricultural Immunology 7, no. 2 (1995): 139–51. http://dx.doi.org/10.1080/09540109509354873.

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11

Liu, Biing-Hui, Feng-Yih Yu, and Fun S. Chu. "Anti-idiotype and Anti-anti-idiotype Antibodies Generated from Polyclonal Antibodies against Microcystin-LR." Journal of Agricultural and Food Chemistry 44, no. 12 (1996): 4037–42. http://dx.doi.org/10.1021/jf960286k.

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12

Ban, N., C. Escobar, R. Garcia, et al. "Crystal structure of an idiotype-anti-idiotype Fab complex." Proceedings of the National Academy of Sciences 91, no. 5 (1994): 1604–8. http://dx.doi.org/10.1073/pnas.91.5.1604.

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13

Brown, SL, RA Miller, SJ Horning, et al. "Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon." Blood 73, no. 3 (1989): 651–61. http://dx.doi.org/10.1182/blood.v73.3.651.651.

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Abstract Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti- idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti- idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

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14

Brown, SL, RA Miller, SJ Horning, et al. "Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon." Blood 73, no. 3 (1989): 651–61. http://dx.doi.org/10.1182/blood.v73.3.651.bloodjournal733651.

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Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti- idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti- idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

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15

Bhattacharya-Chatterjee, Malaya, Sunil K. Chatterjee, and Kenneth A. Foon. "Anti-idiotype vaccine against cancer." Immunology Letters 74, no. 1 (2000): 51–58. http://dx.doi.org/10.1016/s0165-2478(00)00249-2.

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16

Hsu, Kuo-Hui, and Fun S. Chu. "Production and Characterization of Anti-idiotype and anti-anti-idiotype Antibodies from a Monoclonal Antibody against Aflatoxin." Journal of Agricultural and Food Chemistry 42, no. 10 (1994): 2353–59. http://dx.doi.org/10.1021/jf00046a052.

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17

Abu-Shakra, M., and Y. Shoenfeld. "Human anti-DNA idiotype (16/6 idiotype): pathogenic role in autoimmunity." Human Antibodies 1, no. 1 (1990): 10–14. http://dx.doi.org/10.3233/hab-1990-1103.

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18

Stevenson, F. K., and G. T. Stevenson. "Therapeutic Strategies for B Cell Malignancies Involving Idiotype-Anti-idiotype Interactions." International Reviews of Immunology 1, no. 3-4 (1986): 303–33. http://dx.doi.org/10.3109/08830188609056611.

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19

Miller, RA, JN Lowder, J. Gralow, T. Meeker, and R. Levy. "In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias." Blood 69, no. 4 (1987): 1249–54. http://dx.doi.org/10.1182/blood.v69.4.1249.1249.

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Abstract The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti- idiotype antibodies.

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20

Miller, RA, JN Lowder, J. Gralow, T. Meeker, and R. Levy. "In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias." Blood 69, no. 4 (1987): 1249–54. http://dx.doi.org/10.1182/blood.v69.4.1249.bloodjournal6941249.

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Abstract:

The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti- idiotype antibodies.

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21

Thompson, R. E., C. R. Hewitt, D. J. Piper, et al. "Competitive idiotype--anti-idiotype immunoassay for adenosine deaminase binding protein in urine." Clinical Chemistry 31, no. 11 (1985): 1833–37. http://dx.doi.org/10.1093/clinchem/31.11.1833.

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Abstract This competitive immunoassay, based on inhibition by antigen of the idiotype-anti-idiotype interaction, detects adenosine deaminase binding protein (ABP), and involves use of monoclonal anti-idiotype antibodies prepared to a monoclonal antibody specific for ABP. The conditions for this new type of competitive immunoassay are investigated. This competitive immunoassay is as sensitive and reproducible as an earlier described "sandwich"-type immunoassay for ABP (Clin Chem 31: 679-683, 1985). Evaluation of urine samples from normal subjects and from patients showed increased concentrations of ABP in patients with renal disease.

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22

Maloney, DG, S. Brown, DK Czerwinski, et al. "Monoclonal anti-idiotype antibody therapy of B-cell lymphoma: the addition of a short course of chemotherapy does not interfere with the antitumor effect nor prevent the emergence of idiotype-negative variant cells." Blood 80, no. 6 (1992): 1502–10. http://dx.doi.org/10.1182/blood.v80.6.1502.1502.

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Abstract The Ig idiotype of B-cell lymphoma can be used as a tumor-specific target. Prior trials with monoclonal anti-idiotype antibodies alone and combined with alpha-interferon have shown significant antitumor activity. In some patients, idiotype-negative tumors emerged after treatment. In this trial, patients with relapsed non-Hodgkin's lymphoma were treated with two identical courses of monoclonal anti-idiotype anti-body therapy. Concurrent with the second course, at a time when idiotype-negative cells were suspected to be proliferating, a pulse dose of chlorambucil was administered. Tumor biopsies obtained before the first and second courses of treatment and at relapse were analyzed for idiotype expression and proliferation. Thirteen patients received 24 courses of antibody with minimal toxicity. Eleven had tumor regression, with 1 complete remission, 8 partial remissions, and 2 minor remissions, with freedom from progression lasting a median of 7 months in responding patients. Idiotype-negative tumor cells appeared in some relapse specimens despite the use of chlorambucil. In retrospect, this was not surprising because there was no increase in the proliferative rate of these tumors at the time the drug was used. Anti-idiotype antibodies continue to demonstrate antitumor activity against B-cell lymphoma with minimal toxicity. The mechanism of the effect is presumed to involve both direct antiproliferative effects of the antibody on the tumor cells as well as indirect, more long-lasting effects on the host. The addition of a mild chemotherapeutic agent in the dose and schedule used here to the second cycle of antibody therapy did not interfere with the antitumor effect, nor did it decrease the emergence of idiotype-negative cells.

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23

Maloney, DG, S. Brown, DK Czerwinski, et al. "Monoclonal anti-idiotype antibody therapy of B-cell lymphoma: the addition of a short course of chemotherapy does not interfere with the antitumor effect nor prevent the emergence of idiotype-negative variant cells." Blood 80, no. 6 (1992): 1502–10. http://dx.doi.org/10.1182/blood.v80.6.1502.bloodjournal8061502.

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The Ig idiotype of B-cell lymphoma can be used as a tumor-specific target. Prior trials with monoclonal anti-idiotype antibodies alone and combined with alpha-interferon have shown significant antitumor activity. In some patients, idiotype-negative tumors emerged after treatment. In this trial, patients with relapsed non-Hodgkin's lymphoma were treated with two identical courses of monoclonal anti-idiotype anti-body therapy. Concurrent with the second course, at a time when idiotype-negative cells were suspected to be proliferating, a pulse dose of chlorambucil was administered. Tumor biopsies obtained before the first and second courses of treatment and at relapse were analyzed for idiotype expression and proliferation. Thirteen patients received 24 courses of antibody with minimal toxicity. Eleven had tumor regression, with 1 complete remission, 8 partial remissions, and 2 minor remissions, with freedom from progression lasting a median of 7 months in responding patients. Idiotype-negative tumor cells appeared in some relapse specimens despite the use of chlorambucil. In retrospect, this was not surprising because there was no increase in the proliferative rate of these tumors at the time the drug was used. Anti-idiotype antibodies continue to demonstrate antitumor activity against B-cell lymphoma with minimal toxicity. The mechanism of the effect is presumed to involve both direct antiproliferative effects of the antibody on the tumor cells as well as indirect, more long-lasting effects on the host. The addition of a mild chemotherapeutic agent in the dose and schedule used here to the second cycle of antibody therapy did not interfere with the antitumor effect, nor did it decrease the emergence of idiotype-negative cells.

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24

Dalgleish, Angus. "Anti-idiotype vaccines tackle colorectal cancer." Lancet 347, no. 9016 (1996): 1682. http://dx.doi.org/10.1016/s0140-6736(96)91500-7.

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25

Chanh, Tran C., Deborah L. Armstrong, and J. F. Hewetson. "Anti-idiotype vaccines against biological toxins." International Journal of Immunopharmacology 13, no. 6 (1991): 712. http://dx.doi.org/10.1016/0192-0561(91)90205-l.

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26

de Cerio, A. López-Díaz, N. Zabalegui, M. Rodríguez-Calvillo, S. Inogés, and M. Bendandi. "Anti-idiotype antibodies in cancer treatment." Oncogene 26, no. 25 (2007): 3594–602. http://dx.doi.org/10.1038/sj.onc.1210371.

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27

Becker, María Inés, Juan E. Aguayo, Adolfo Jamett, et al. "An alternative ELISA for T4 determination based on idiotype anti-idiotype interaction and a latex method for anti-idiotype monoclonal antibody selection." Journal of Immunological Methods 192, no. 1-2 (1996): 73–85. http://dx.doi.org/10.1016/0022-1759(96)00023-3.

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28

Saito, T., and K. Rajewsky. "Helper T cells reacting to idiotype on IgG but not IgM." Journal of Experimental Medicine 162, no. 4 (1985): 1399–404. http://dx.doi.org/10.1084/jem.162.4.1399.

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Immunization with an IgG1 but not an IgM monoclonal anti-NP (4-hydroxy-3-nitrophenyl acetyl) antibody induced idiotype-recognizing T helper cells, although these two antibodies carry the same variable regions. The T cells appear to react to an idiotype on the IgG1 but not the IgM antibody. They selectively enhance the expression of that idiotype in the IgG1 fraction of an in vitro anti-NP response.

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29

Vakil, Meenal, and John F. Kearney. "Functional Relationship Between T15 and J558 Idiotypes in BALB/c Mice." Developmental Immunology 1, no. 3 (1991): 213–24. http://dx.doi.org/10.1155/1991/91729.

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In inbred strains of mice, antiphosphorylcholine (PC) and anti-α1,3 dextran (DEX). antibodies are structurally distinct from each other and have been shown to exhibit noncrossreactive antigen binding and idiotypic specificities. However, the prototype anti-PC and anti-DEX antibodies, TEPC15 and J558, respectively, were shown to be connected via a common autoantiidiotypic monoclonal antibody isolated from newborn BALB/c mice. The capacity of various monoclonal anti-PC and anti-DEX antibodies as well as the antigens PC and DEX to modulate T15 and J558 idiotypes in BALB/c mice was tested by their administration to newborn mice. Anti-PC antibodies of the .T15 idiotype injected into 2-4-day-old mice, at a time when T15 anti-PC precursors develop in BALB/c mice, suppressed the anti- PC response of these mice at 6 weeks of age. Similarly, J558 antibodies injected into 8-12-day-old mice, at a time when J558 precursors normally develop, suppressed the response to DEX. As a further demonstration of this connectivity, the injection of J558 into 4-day-old mice led to a down modulation of T15 idiotype, whereas both T15 and a minor idiotypeexpressing antibody M167 when injected into 8-12-day-old mice caused a reduction in expression of the J558 idiotype. As predicted from in vitro analysis, injection of anti-PC antibodies of the M167 idiotype 2 to 4 days after birth enhanced the subsequent response to PC. However, anti-PC antibodies expressing another minor M603 idiotype did not affect the PC. response. The results parallel thein vitroenhancement of M167 antibodies but not M603 on T15 binding to antiidiotypein vitro. Similarly, anti-DEX antibodies expressing the M104E idiotype had no detectable effects on the capacity to respond to PC or DEX or on the expression of T15 and J558 idiotypes as adults. Exposure of newborn mice to PC led to a dramatic reduction in the response to DEX as adults, whereas exposure to DEX at this stage of development had no effect on response to PC as adults. Collectively, these observations provide evidence for a complex functional connectivity between T15 and J558 idiotype-bearing B cells during ontogeny and extend our previous observations that development of these idiotypes is regulated by idiotype-directed interactions between B cells or their immunoglobulin products.

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30

Borden, Paula, and Elvin A. Kabat. "An immunochemical analysis of precipitating and non-precipitating idiotype-anti-idiotype reactions." Molecular Immunology 27, no. 6 (1990): 487–94. http://dx.doi.org/10.1016/0161-5890(90)90067-a.

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31

Varghese, Bindu, Behnaz Taidi, Adam Widman, James Do, and R. Levy. "Generation of CD8 T Cell-Mediated Protective Immunity against Tumor Escapees." Blood 112, no. 11 (2008): 2623. http://dx.doi.org/10.1182/blood.v112.11.2623.2623.

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Abstract Introduction: Anti-idiotype antibodies against B cell lymphoma have shown remarkable success in causing tumor regression in the clinic. In addition to their known ability to mediate ADCC, anti-idiotype antibodies have also been shown to directly inhibit the proliferation of tumor cells by sending negative growth signals via the target idiotype. However, further studies to investigate this mechanism have been hindered by the failure of patient tumor cells to grow ex vivo. Methods and Results: In order to study this phenomenon further, we developed an antibody against the idiotype on an A20 mouse B lymphoma cell line. A radioactive thymidine incorporation assay showed decreased A20 cell proliferation in the presence of the anti-id antibody ex vivo. In vivo, when mice were treated intraperitoneally (i.p.) with 100 μg of antibody 3 hours post-tumor inoculation (1×106 A20 subcutaneously (s.c.)), tumor growth was delayed for greater than 40 days after which the tumor began to grow once again. Further analysis of these escaping tumor cells by flow cytometry showed that that the tumor cells escaped the antibody-mediated immune response by down-regulating expression of idiotype and IgG on their surfaces although the cells retained idiotype expression intracellularly. This down-regulation of surface idiotype rendered the tumor cells resistant to both ADCC and signaling-induced cell death. The addition of an immunostimulatory bacterial mimic (CpG-DNA; 100 μg × 5 intratumoral (i.t.) injections; Days 2, 3 4, 6 & 8) to antibody therapy (Day 0; 100 μg i.p.) cured large established tumors (Day 0 = 1 cm2) and prevented the occurrence of tumor escapees (p&lt;0.0001). Antibody plus CpG combination therapy in tumor-bearing mice deficient for CD8+ T cells demonstrated the critical role of CD8+ T cells in A20 tumor eradication (p&lt;0.005). Depletion of CD4+ T cells was found to have no significant impact on the therapy. We also found that when mice were inoculated with two tumors and treated with anti-idiotype antibody (i.p.) followed by intratumoral CpG in just one tumor (Day 0=1 cm2; anti-idiotype antibody 100 μg Day 0; 100 μg CpG Days 2, 3, 4, 6 & 8), untreated tumors regressed just as well as CpG-treated tumors indicating a systemic anti-tumor immune response was generated. Conclusion: Anti-idiotype therapy, although effective in delaying tumor growth, frequently generates antigen-loss variants. However, we found that when anti-idiotype antibodies were combined with CpG, even large established tumors were cured due to systemic CD8+ T cell-dependent tumor immunity. Rather than simply mediating ADCC against a single tumor antigen, which requires the constant infusion of antibody to hamper tumor growth, we hypothesize a cytotoxic T-cell response against many tumor antigens was also generated. Such a diverse T-cell repertoire can prevent the emergence of tumor escapees and collectively provide long-lasting tumor protection. These pre-clinical results suggest that anti-tumor antibodies combined with CpG warrant further study in patients with B cell lymphoma.

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Navarrete, Marcelo A., Kristina Heining-Mikesch, Cristina Bertinetti-Lapatki, Marcus Duehren-von Minden, Andrea Hafkemeyer, and Hendrik Veelken. "Idiotype Vaccination of Untreated Indolent B-Cell Lymphoma: Durable Objective Remissions and Association of Superior Outcome with Cellular Immune Responses." Blood 112, no. 11 (2008): 235. http://dx.doi.org/10.1182/blood.v112.11.235.235.

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Abstract Idiotype vaccination refers to active immunization of B-cell lymphoma (B-NHL) patients with the clonal immunoglobulin (Ig) expressed by the tumor cells. After systemic cytoreductive therapy, idiotype vaccination has been shown to induce specific cellular and humoral immune responses; and humoral responses in particular are associated with prolonged remission and encouraging survival rates. Conventional idiotype vaccines are composed of the entire lymphoma-derived Ig coupled to the immunogenic carrier KLH and are administered subcutaneously with adjuvant. We have developed a idiotype production strategy based on bacterial expression of the lymphoma-derived idiotype as a recombinant Fab fragment (Bertinetti et al., EJH 2006). Intradermal administration of this antigen with lipid-based adjuvant and subcutaneous coadministration of GM-CSF had excellent immunogenicity in a phase I trial of advanced, heavily pretreated B-NHL patients (Bertinetti et al., Cancer Research 2006). In a subsequent phase II trial, 20 patients with untreated indolent B-NHL (14 follicular [FL], 3 nodal marginal zone [nMZL], 3 mantle cell [MCL]) and without immediate need for cytoreduction received at least 6 monthly idiotype vaccinations. No grade IV toxicities were seen, and the sole case of grade III toxicity, generalized erythema, did not preclude completion of the vaccination schedule. Prior to vaccination, 5/19 patients (26%) had decreased CD4+ and 6/19 patients (31%) low CD8+ T cells counts. Furthermore, 10/12 anti-HbS-negative patients (83%) failed to mount a detectable immune response to a conventional hepatitis B vaccine administered concomitantly to idiotype vaccination. Despite this functional immunodeficiency, 12/18 analyzed patients (66%) developed a cellular immune response to idiotype as detected by enumeration of IFNgamma-secreting cells by DC-ELISpot. The ELISpot protocol was validated by blinded interlaboratory testing (www.cimt.de). The frequency of idiotype-responding T cells increased from the 2nd to the 6th vaccination and could be effectively boostered by maintenance immunization in 3-monthly intervals. In vitro stimulation of PBMC from responding patients with idiotype induced specific proliferation of CD4+ T-cells and a shift towards a Th1 response in post-vaccination samples. In addition, 8/18 analyzed patients (44%) developed anti-idiotype IgG or IgM antibodies as assessed by ELISA, and the combined immune response rate was 85%. After a median follow-up of 34 months, 8 patients (40%) are progression-free, and 10 (50%) did not require cytoreductive therapy. Cellular immune responses were associated with superior PFS (p&lt;0.05), and 5 of 6 non-responders eventually required cytoreductive therapy. Humoral immune responses were not related to PFS. Six patients (30%; only FL or nMZL) achieved an objective partial remission, including near-complete disappearance of a large submandibular mass and one subcutaneous lymphoma mass. All objective responders developed specific cellular immunity, but only 4 anti-idiotype antibodies. Five patients are in continuing remission for 12–49 months. Intradermal immunization with the chosen idiotype formulation has excellent immunogenicity despite a severely impaired immune function in untreated B-NHL patients. Furthermore, this is the first active immunotherapy trial showing objective and durable lymphoma responses in first-line therapy at a higher rate than expected for spontaneous remissions. In this setting, and in contrast to conventional idiotype vaccination schedules, cellular anti-idiotype immunity may play a crucial role for a favorable clinical outcome. Since passive humoral anti-lymphoma immunity can be easily transferred by infusions of commercially available monoclonal antibodies, synergistic benefit may be envisioned for an initial vaccination course aimed to prime anti-idiotype T-cells combined with subsequent passive immunotherapy.

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33

Navarrete, Marcelo A., Kristina Heining-Mikesch, Frank Schüler, et al. "Upfront immunization with autologous recombinant idiotype Fab fragment without prior cytoreduction in indolent B-cell lymphoma." Blood 117, no. 5 (2011): 1483–91. http://dx.doi.org/10.1182/blood-2010-06-292342.

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Abstract Idiotype vaccination for follicular lymphoma is primarily being developed as remission consolidation after chemotherapy. We investigated idiotype vaccination as primary intervention for treatment-naive indolent B-cell lymphoma and in a separate cohort as remission consolidation after chemotherapy to assess immunization-induced immune responses in relation to progression-free survival (German Clinical Trials Register, DRKS00000227). Twenty-one patients in each cohort received 6 intradermal injections of adjuvanted recombinant idiotype Fab fragment (FabId); 76% of patients in both groups developed anti-idiotype antibodies and/or cellular immunity as measured by enzyme-linked immunosorbent assay and interferon-γ ELISpot. In treatment-naive patients, only cellular responses correlated with superior progression-free survival (P < .002) and durable objective remissions (P = .04). Immunization-induced T cells recognized hypermutated or complementarity-determining region 3 epitopes. After remission consolidation immunization, induction of anti-idiotype antibodies correlated with progression-free survival. Low B-cell counts after rituximab therapy predicted for failure to develop anti-idiotype antibodies. These results are similar to published trials showing an association of humoral immunity with control of residual lymphoma. In contrast, effective immunity against untreated lymphoma appears to be dependent on idiotype-specific T cells. Sustained remissions in patients with vaccination-induced cellular immunity suggest clinical benefit and warrant a randomized comparison of this vaccine with expectant management for asymptomatic follicular lymphoma.

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34

Kollet, Orit, Joseph Haimovich, and Nurit Hollander. "Idiotype-specific inhibition of LFA-1-mediated cell adhesion by anti-idiotype×anti-LFA-1 bispecific antibodies." Immunology Letters 62, no. 3 (1998): 171–76. http://dx.doi.org/10.1016/s0165-2478(98)00045-5.

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35

Torchia, James, Kipp Weiskopf, and Ronald Levy. "Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies." Proceedings of the National Academy of Sciences 113, no. 19 (2016): 5376–81. http://dx.doi.org/10.1073/pnas.1603335113.

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B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor (BCR), otherwise known as idiotype. The tumor idiotype differs, however, from patient to patient, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype by using a semisynthetic personalized therapeutic that is more practical to produce on a patient-by-patient basis than monoclonal antibodies. In this method, a small peptide with affinity for a tumor idiotype is identified by screening a library, chemically synthesized, and then affixed to the amino terminus of a premade IgG Fc protein. We demonstrate that the resultant semisynthetic anti-idiotype peptibodies kill tumor cells in vitro with specificity, trigger tumor cell phagocytosis by macrophages, and efficiently clear human lymphoma in a murine xenograft model. This method could be used to target tumor with true precision on a personalized basis.

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Rajadhyaksha, Manoj, Yu-Fang Yang, and Yasmin M. Thanavala. "Immunological evaluation of three generations of anti-idiotype vaccine: study of B and T cell responses following priming with anti-idiotype, anti-idiotype peptide and its MAP structure." Vaccine 13, no. 15 (1995): 1421–26. http://dx.doi.org/10.1016/0264-410x(95)00072-9.

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Ai, Weiyun Z., Robert Tibshirani, Behnaz Taidi, Debra Czerwinski, and Ronald Levy. "Anti-idiotype antibody response after vaccination correlates with better overall survival in follicular lymphoma." Blood 113, no. 23 (2009): 5743–46. http://dx.doi.org/10.1182/blood-2009-01-201988.

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Abstract Previous studies demonstrated that vaccination-induced tumor-specific immune response is associated with superior clinical outcome in patients with follicular lymphoma. Here, we investigated whether this positive correlation extends to overall survival (OS). We analyzed 91 untreated patients who received CVP chemotherapy (cyclophosphamide, vincristine, and prednisone) followed by idiotype vaccination. Idiotype proteins were produced either by the hybridoma method or by expression of recombinant idiotype-encoding sequences in mammalian or plant-based expression systems. We found that achieving a complete response/complete response unconfirmed (CR/CRu) to CVP and making an anti-idiotype antibody are 2 independent factors that each correlated with longer OS at 10 years (89% vs 68% with or without a CR/CRu, P = .024; 90% vs 69% with or without tumor-specific antibody production; P = .027). In the subset of patients who received hybridoma-generated vaccines, we found that anti-idiotype production was even more highly associated with superior OS (P < .002); this was the case even in patients with a partial response (PR) to CVP (P < .001).

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POSKITT, D. C., M. J. B. JEAN-FRANCOIS, S. TURNBULL, L. MACDONALD, and D. YASMEEN. "The nature of immunoglobulin idiotypes and idiotype-anti-idiotype interactions in immunological networks." Immunology and Cell Biology 69, no. 2 (1991): 61–70. http://dx.doi.org/10.1038/icb.1991.11.

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Sharpe, Richard J. "A tumor immunotherapy technique based on modulation of the idiotype anti-idiotype network." Medical Hypotheses 18, no. 3 (1985): 281–87. http://dx.doi.org/10.1016/0306-9877(85)90029-5.

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Niwa, Toshifumi, Takayuki Kobayashi, Pi Sun, Junichi Goto, Hiroyuki Oyama, and Norihiro Kobayashi. "An enzyme-linked immunometric assay for cortisol based on idiotype–anti-idiotype reactions." Analytica Chimica Acta 638, no. 1 (2009): 94–100. http://dx.doi.org/10.1016/j.aca.2009.02.010.

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Berenson, JR, A. Lichtenstein, S. Hart, D. Palomares, and RA Miller. "Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance." Blood 75, no. 11 (1990): 2107–11. http://dx.doi.org/10.1182/blood.v75.11.2107.2107.

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Abstract Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

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Berenson, JR, A. Lichtenstein, S. Hart, D. Palomares, and RA Miller. "Expression of shared idiotypes by paraproteins from patients with multiple myeloma and monoclonal gammopathy of undetermined significance." Blood 75, no. 11 (1990): 2107–11. http://dx.doi.org/10.1182/blood.v75.11.2107.bloodjournal75112107.

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Twenty-nine murine monoclonal antibodies have been produced that react with shared idiotypes expressed by B-cell lymphomas and leukemias. We tested this panel of antibodies for reactivity with the paraproteins from 32 patients with multiple myeloma and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). Thirteen of 42 paraproteins reacted with at least one antibody in this panel of anti- idiotypic antibodies. Six different anti-idiotypes demonstrated reactivity with the paraproteins. A similar frequency of reactivity was found for both myeloma and MGUS proteins. One antibody, S30–47, reacted with 6 of 32 (19%) of the paraproteins from patients with multiple myeloma, whereas this anti-idiotype only bound to 3% of non-Hodgkin's B- cell lymphomas and no cases of chronic lymphocytic leukemia. This anti- idiotype reacted with both components of a biphenotypic paraprotein (IgG kappa and IgG lambda) in one patient. In each of nine patients tested, plasma cells isolated from bone marrow were shown to be reactive with the same anti-idiotype we found to react with the paraprotein. Antishared idiotype antibodies may provide useful reagents for studies of patients with monoclonal gammopathies.

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ZHANG, Li-Ning, Mao-Guo GONG, Li-Cheng JIAO, and Wen-Ping MA. "Clonal Selection Algorithm Based on Anti-Idiotype." Journal of Software 20, no. 5 (2010): 1269–81. http://dx.doi.org/10.3724/sp.j.1001.2009.03266.

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&NA;. "105AD7: an anti-idiotype colorectal cancer vaccine." Inpharma Weekly &NA;, no. 1042 (1996): 8. http://dx.doi.org/10.2165/00128413-199610420-00014.

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&NA;. "Anti-idiotype colorectal cancer vaccine 105AD7 immunogenic." Inpharma Weekly &NA;, no. 1235 (2000): 6. http://dx.doi.org/10.2165/00128413-200012350-00015.

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HERLYN, DOROTHEE, JAN ZALOUDIK, RAJASEKHARAN SOMASUNDARAM, LUTZ JACOB, ANDREA BENDEN, and MICHAEL MASTANGELO. "Anti-Idiotype Vaccine in Colorectal Cancer Patients." Hybridoma 12, no. 5 (1993): 515–20. http://dx.doi.org/10.1089/hyb.1993.12.515.

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Grzych, J. M., M. Capron, P. H. Lambert, C. Dissous, S. Torres, and A. Capron. "An anti-idiotype vaccine against experimental schistosomiasis." Nature 316, no. 6023 (1985): 74–76. http://dx.doi.org/10.1038/316074a0.

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Bendandi, M. "Anti-idiotype vaccines for human follicular lymphoma." Leukemia 14, no. 8 (2000): 1333–39. http://dx.doi.org/10.1038/sj.leu.2401861.

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Bhattacharya-Chatterjee, Malaya, Sunil K. Chatterjee, and Kenneth A. Foon. "Anti-idiotype antibody vaccine therapy for cancer." Expert Opinion on Biological Therapy 2, no. 8 (2002): 869–81. http://dx.doi.org/10.1517/14712598.2.8.869.

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Herlyn, D., Rajasekharan Somasundaram, Weiping Li, and Haruhiko Maruyama. "Anti-idiotype cancer vaccines: past and future." Cancer Immunology, Immunotherapy 43, no. 2 (1996): 65–76. http://dx.doi.org/10.1007/s002620050305.

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Journal articles on the topic 'Anti-idiotype'

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