Academic literature on the topic 'Christoph Spurk's functional model'

The aim of the article is to shed light upon the essence and functions of the civil society, as well as to outline the features of its functioning. The article considers the views of thinkers of the past and modernity on the essence and significance of civil society, which formed the basis of a modern understanding of its content and role in the development of democracy and society. Also, modern approaches to the interpretation of the content of this concept were reviewed. It is revealed, that those approaches to the interpretation of the civil society of thinkers of the past and present, which take into account its component as economy, were and remain the most studied and time-consuming ones, and eventually do not lose their relevance. The main functional models of civil society are highlighted. It is justified, that the extended functional model, formed on the basis of the models of Merkel-Lauth and Edwards, more fully reflects the functions, performed by the civil society. Different models of interaction of civil society, state, business, family are investigated. It is proposed to consider the civil society as an environment that enables the interaction of the state, business and family in accordance with their natural functioning

Ready-to-use oxygen gradient microplates for customized in vitro assays for the phenotypic and functionalcharacterization of primary macrophages in immuno-oncology drug developmentChristoph Schifflers1, Martijn Vlaming1, Emmanuelle Sidot1, Jezabel Lefèvre1, Elise Pepermans2, EllenBoelen1, Enrico Grassili2 and Sofie Pattyn11IQVIA Laboratories, In Vitro Immunology (formerly known as ImmunXperts), Rue Clément Ader 10, 6041Gosselies Belgium2ImmuneSpec, Galileilaan 18 bus 6, 2845 Niel, Belgium3InSimili srl, Viale Giuseppe Fanin 48, Bologna, 40050, ItalyOxygen level fluctuations in tumor micro-environment (TME) can alter the phenotype and function ofcancer cells as well as tumor-infiltrating immune cells, such as macrophages. For the functional evaluationof new immuno-oncology drug candidates, it can be key to take into consideration the effects of varyingO2 concentrations. In fact, it is well established that varying oxygen concentrations and tumor hypoxia candrive treatment resistance and cancer recurrence. Modeling this layer of functional complexity of thetumor microenvironment, typically requires the use of animal models or tumoroid systems which can becomplex to establish, time-consuming and expensive. InSimili developed a new technology that providesready-to-use microplates that model spatially controlled O2 levels at fixed O2 concentrations or O2 gradients(adaptable for individual wells). Combining this technology with highly optimized in vitro assays using highquality primary immune cells can provide a useful tool with improved predictive value for the cost-effectivefunctional characterization and lead selection of new immuno-oncology drug candidates.In this study, the impact of varying O2 concentrations (ranging from 20% to 1% O2) was assessed usingcustomized microplates on the phenotype of macrophages derived from healthy donor PBMCs.Furthermore, the impact of different O2 concentration on the capacity of M2-like macrophages to suppress T cell activation was explored. Finally, the impact of several oxygen concentrations on the reprogrammingof M2-like macrophages was evaluated.Taken together, this study showed that InSimili’s plates provide a ready-to-use tool that can be used incustomized in vitro assays to model varying O2 concentrations. Integrating this technology with highlycustomized in vitro bioassays can serve as a valuable tool for immuno-oncology drug development whiletaking into account an additional degree of the complexity of the TME in 2D and 3D systems. Citation Format: Christoph Schifflers, Martijn Vlaming, Emmanuelle Sidot, Jezabel Lefevre, Elise Pepermans, Ellen Boelen, Enrico Grassilli, Sofie Pattyn. Ready-to-use oxygen gradient microplates for customized in vitro assays for the phenotypic and functional characterization of primary macrophages in immuno-oncology drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2199.

Abstract Physiologically relevant in vitro tumor models are crucial in any research setting from preclinical drug development to functional precision oncology. Patient-derived 3D cell culture models (PD3D®) are validated cancer models which recapitulate the biology of the original tumor tissue. PD3D® can be used to model intratumoral heterogeneity in medium and high throughput screens. Using a reverse clinical engineering approach, PD3D® models are already applied in personalized oncology to identify treatment for an individual patient. We successfully established a living biobank of more than 500 PD3D® models, spanning from common cancers like colorectal, breast (incl. TNBC), non-small cell lung and pancreatic carcinoma, to orphan indications including various subtypes of sarcomas. Not surprisingly, PD3D® model morphology and culture requirements differ between tumor entities. Treating PD3D® models with standard of care drugs in a semi-automated high-throughput assay, we observed heterogeneity in drug sensitivity between models of the same cancer type, recapitulating clinical response of patients. Combining drug sensitivity profiles with genomic and proteomic data of the same PD3D® models, we successfully identified a biomarker for predicting chemosensitivity towards MEK-targeting drugs. For application of PD3D® in truly personalized oncology, we developed a protocol that allows us to generate a PD3D® culture and perform a drug sensitivity assay for an individual patient within a therapy-relevant timeframe. Within 38 days we identified a systemic therapy for a young patient with a relapsed metastasized synovial sarcoma. After surgery and initiation of recommended chemotherapy, the patient is now under remission. To further expand the scope of PD3D® for therapy response prediction, we established a method for irradiation of PD3D® cultures with different dosages of photon and proton radiation. We observed significant, model specific differences in radiosensitivity between PD3D® sarcoma models which also reflect clinically heterogenous responses. Additionally, PD3D® models can be employed for a tumor organoid-on-chip platform (TumOC), delivering real-time information on physiological parameters like drug response-mediated oxygen consumption in a microfluidic system. In conclusion, PD3D® models act as jacks-of-all-trades in current and future cancer research, delivering robust and reliable data that not only is of academic value, but speeds up the drug development process, and are ready for prime time in functional precision oncology. Citation Format: Lena Wedeken, Samantha Forbrig, Katja Herrera-Glomm, Juergen Loskutov, Ulrike Pfohl, Irina Piven, Michael Poehle, Manuela J. Regenbrecht, Barbara Seller, Cynthia Yapto, Sabine Finkler, Larissa Ruhe, Quirin Graf Adelmann, Christoph Reinhard, Marie Flechner, Katja Uhlig, David Kaul, Siyer Roohani, Maya Niethard, Rica Sauer, Christian R. Regenbrecht. PD3D®models as jacks-of-all-trades for cancer research and therapy response prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4235.

Abstract T cells play a central role in immune responses against cancer. Within the tumor, however, T cells are exposed to a plethora of inactivating factors causing various degrees of dysfunction, changes in metabolism and a generally reduced cellular fitness, eventually leading to tumor progression. To prevent or delay the onset of exhaustion and instead augment effector functions and persistence of functional T cells, costimulatory factors and cytokines are needed. Targeting 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, has been shown to represent a promising strategy for inducing an activating signal in CD8+ T cells, resulting in increased pro-inflammatory cytokine secretion, cytotoxic function, and survival. Engineered arenavirus vectors based on lymphocytic choriomeningitis virus (LCMV) or Pichinde virus (PICV) have been shown previously to induce massive infiltration of tumor antigen specific CD8+ T cells into the tumor in several preclinical cancer models. To investigate whether enhanced co-stimulation via 4-1BB further improves T cell responses and/or tumor control, combination therapies with replicating LCMV based vectors (artLCMV) and 4-1BB agonists were explored. A single intravenous treatment of artLCMV encoding the tumor associated antigens (TAA) gp70 or Trp2 in B16.F10 tumor bearing mice induced TAA specific CD8+ T cells in both the periphery and the tumor, resulting in tumor growth delay and some complete responses. Combining artLCMV with agonistic anti-4-1BB significantly improved tumor control and increased the number of complete responders. Analysis of tumor infiltrating lymphocytes revealed higher absolute numbers of TAA specific CD8+ T cells in the combination group compared to the artLCMV alone group. Analyses of the TAA specific cells revealed that more cells expressed granzyme B, Ki67 and Bcl-XL when co-stimulated with anti-4-1BB compared to the group treated with artLCMV alone. Importantly, encoding 4-1BBL in addition to a TAA in artLCMV revealed similar outcomes as just summarized for the combination with agonistic antibodies. Overall, these experiments confirmed the strong antigenicity and T cell inducing capacity of the engineered arenavirus platform, leading to efficient tumor control in a stringent mouse model. Combination with 4-1BB agonists, either in form of antibodies or encoded within the vector genome, was shown to further augment TAA-specific T cell responses within the tumor, leading to better tumor growth control and a higher rate of complete responders. Citation Format: Judith Strauss, Marilies Scheinost, Theresa Kleissner, Diana Reckendorfer, Kimberly Pojar, Mohamed Habbeddine, Sarah Ahmadi-Erber, Daniela Deutschmann, Sarah Schmidt, Josipa Raguz, Igor Matushansky, Christoph Lampert, Klaus K. Orlinger, Henning Lauterbach. Evaluation of a cancer immunotherapy with engineered arenavirus vectors and 4-1BB agonists in a preclinical tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4198.

Abstract The molecular mechanisms governing invasion, dissemination, extravasation, and early metastatic colonization remain incompletely understood. In the BALB-neuT mouse model, we found that most metastases originate from disseminated cancer cells (DCCs) that left the primary site early in tumorigenesis, i.e. when lesions are still small. Consequently, we investigated whether cellular density and the tumor microenvironment synergize to generate the plasticity needed during metastasis. RNA-sequencing analyses of murine breast cancer cells in low cellular density (LD) and high cellular density (HD) conditions revealed distinct profiles of differentially expressed genes. Notably, we identified the enrichment of ribosomal RNA (rRNA) and chromatin remodeling pathways in LD conditions. Interestingly, once these cells were treated with Wnt4 and Rankl, factors secreted by the tumor microenvironment, the expression profile of genes involved in proliferation, migration and stemness as well as epigenetic-related factors changed drastically. Specifically, cells in LD conditions treated with Wnt4 and Rankl displayed induced migration and stemness phenotypes, whereas under HD conditions, these signals induced proliferation. Among the chromatin-remodeling pathways, we found that BAZ2A along with the rRNA regulating network were primarily upregulated in migratory cancer cells. Immunostaining of primary and metastatic lesions in murine and human breast cancer samples showed an upregulation of BAZ2A in early/microlesions compared to more advanced and proliferative macroscopic lesions. Taken together, these results indicate that cell density, tumor microenvironmental factors and BAZ2A-containing chromatin regulating complexes play pivotal roles in regulating cancer cell plasticity in breast cancer. Additional sequencing and functional analyses will be performed to dissect the specific components of this mechanism and evaluate their impact on the in vivo colonization of breast cancer models. Citation Format: Miriam Kokal-Ribaudo, Nora Jahnen, Saba Sameri, Fulvia Ferrazzi, Renato Liguori, Christoph A. Klein, Gernot Längst, Hedayatollah Hosseini. Tumor microenvironment-mediated regulation of early dissemination and colonization in breast cancer via BAZ2A-containing remodeling complexes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1504.

"Das Rechtssystem geht davon aus, dass der Mensch – und nur der Mensch – eine natürliche Person ist. Das sei ein Irrtum, argumentiert Malte-Christian Gruber, denn die Rechtssubjektivität wird keineswegs alleine mit dem bloßen Menschsein begründet. Es ist die sittliche Autonomie, die den Menschen zu einem »Subjekt, dessen Handlungen einer Zurechnung fähig sind« (Kant) und mithin zur Person macht. Personen werden nicht mit dem Menschsein als solchem identifiziert, sondern durch die Zuschreibung von Handlungs- und Rechtsträgerschaft. Eine solche funktionale Vorstellung von Rechtssubjektivität ist prinzipiell auch dazu imstande, neben Menschen noch weitere autonome Agenten als Träger von Rechten und Pflichten ein- zusetzen, z.B. technische Artefakte und andere nicht-menschliche Agenten. Christoph Menke macht dagegen darauf aufmerksam, dass die Erfindung neuer Rechte das eigentliche Bewegungsgesetz der politischen Emanzipation in der Moderne war. Das begann mit den bürgerlichen Revolutionen und ist immer noch das generelle Modell, mit dem Politik und Theorie operieren, die neue Rechte für nicht-menschliche Lebewesen und Artefakte einfordern. So wie im 19. und 20. Jahrhundert die rechtliche Emanzipation zunächst über die Grenzen bürgerlicher Subjektivität hinausgeführt hat und soziale und kulturelle Rechte erfand, so sollen wir nun den weiteren, konsequenten Schritt tun und auch noch die Bindung der juridischen Anerkennung an die Kategorie menschlicher Subjektivität aufbrechen. Auch Bio- und Artefakte sollen als eigenständige Rechtssubjekte rekonstruiert werden. Es fehlt ihnen allerdings etwas, das in den emanzipatorischen Kämpfen der Vergangenheit schlechthin grundlegend war: Ein Träger von Rechten zu sein, hieß, ein Fordernder von Rechten, ja, ein Kämpfer für Rechte gewesen zu sein. Man konnte keine rechtliche Person als Träger von Rechten sein, ohne ein politisches Subjekt als Kämpfer und Denker von Rechten gewesen zu sein. Wenn die Bindung der rechtlichen Personalität an die menschliche Subjektivität aufgelöst wird, damit es Bio- und Artefakt-Rechte geben kann, löst sich zugleich auch diese Einheit von rechtlicher Personalität und politischer Subjektivität auf, die die moderne Idee der Rechte definiert hatte. The legal system assumes that human beings – and only human beings – are natural persons. That is erroneous, argues Malte-Christian Gruber, because legal subjectivity isn’t founded in humanity alone. It is moral autonomy that makes man into a “subject whose actions are capable of attribution” (Kant) and thus into a person. Personhood is not identified with being human as such, but by the attribution of actions and legal ownership. Besides human beings, such a functional concept of legal subjectivity can in principle also be applied to other autonomous agents as holder of rights and obligations, e.g. techno- logical artifacts and other non-human agents. Christoph Menke in turn points out that the invention of new rights was the actual law of motion of political emancipation in modern times. This began with the bourgeois revolutions and is still the general model with which politics and theory operate to claim new rights for non-human creatures and artifacts. Just as in the 19th and 20th centuries, the legal emancipation initially led beyond the limits of bourgeois subjectivity and in- vented social and cultural rights, so should we make a further consequent step and break with the dependence of juridical recognition on the category of human subjectivity. Also bio- and artifacts are to be reconstructed as independent legal entities. However, they lack something that was absolutely fundamental in the emancipatory struggles of the past: to be a subject of rights meant to have demanded rights, indeed, to have been a fighter for rights. One could not be a legal person and holder of rights without having been a political subject as fighter and thinker of rights. To suspend the dependence of legal personhood on human subjectivity so that there may be bio- and artifact-rights also means to dissolve the unity between legal personality and political subjectivity that once defined the modern idea of rights. "

"Das Rechtssystem geht davon aus, dass der Mensch – und nur der Mensch – eine natürliche Person ist. Das sei ein Irrtum, argumentiert Malte-Christian Gruber, denn die Rechtssubjektivität wird keineswegs alleine mit dem bloßen Menschsein begründet. Es ist die sittliche Autonomie, die den Menschen zu einem »Subjekt, dessen Handlungen einer Zurechnung fähig sind« (Kant) und mithin zur Person macht. Personen werden nicht mit dem Menschsein als solchem identifiziert, sondern durch die Zuschreibung von Handlungs- und Rechtsträgerschaft. Eine solche funktionale Vorstellung von Rechtssubjektivität ist prinzipiell auch dazu imstande, neben Menschen noch weitere autonome Agenten als Träger von Rechten und Pflichten ein- zusetzen, z.B. technische Artefakte und andere nicht-menschliche Agenten. Christoph Menke macht dagegen darauf aufmerksam, dass die Erfindung neuer Rechte das eigentliche Bewegungsgesetz der politischen Emanzipation in der Moderne war. Das begann mit den bürgerlichen Revolutionen und ist immer noch das generelle Modell, mit dem Politik und Theorie operieren, die neue Rechte für nicht-menschliche Lebewesen und Artefakte einfordern. So wie im 19. und 20. Jahrhundert die rechtliche Emanzipation zunächst über die Grenzen bürgerlicher Subjektivität hinausgeführt hat und soziale und kulturelle Rechte erfand, so sollen wir nun den weiteren, konsequenten Schritt tun und auch noch die Bindung der juridischen Anerkennung an die Kategorie menschlicher Subjektivität aufbrechen. Auch Bio- und Artefakte sollen als eigenständige Rechtssubjekte rekonstruiert werden. Es fehlt ihnen allerdings etwas, das in den emanzipatorischen Kämpfen der Vergangenheit schlechthin grundlegend war: Ein Träger von Rechten zu sein, hieß, ein Fordernder von Rechten, ja, ein Kämpfer für Rechte gewesen zu sein. Man konnte keine rechtliche Person als Träger von Rechten sein, ohne ein politisches Subjekt als Kämpfer und Denker von Rechten gewesen zu sein. Wenn die Bindung der rechtlichen Personalität an die menschliche Subjektivität aufgelöst wird, damit es Bio- und Artefakt-Rechte geben kann, löst sich zugleich auch diese Einheit von rechtlicher Personalität und politischer Subjektivität auf, die die moderne Idee der Rechte definiert hatte. The legal system assumes that human beings – and only human beings – are natural persons. That is erroneous, argues Malte-Christian Gruber, because legal subjectivity isn’t founded in humanity alone. It is moral autonomy that makes man into a “subject whose actions are capable of attribution” (Kant) and thus into a person. Personhood is not identified with being human as such, but by the attribution of actions and legal ownership. Besides human beings, such a functional concept of legal subjectivity can in principle also be applied to other autonomous agents as holder of rights and obligations, e.g. techno- logical artifacts and other non-human agents. Christoph Menke in turn points out that the invention of new rights was the actual law of motion of political emancipation in modern times. This began with the bourgeois revolutions and is still the general model with which politics and theory operate to claim new rights for non-human creatures and artifacts. Just as in the 19th and 20th centuries, the legal emancipation initially led beyond the limits of bourgeois subjectivity and in- vented social and cultural rights, so should we make a further consequent step and break with the dependence of juridical recognition on the category of human subjectivity. Also bio- and artifacts are to be reconstructed as independent legal entities. However, they lack something that was absolutely fundamental in the emancipatory struggles of the past: to be a subject of rights meant to have demanded rights, indeed, to have been a fighter for rights. One could not be a legal person and holder of rights without having been a political subject as fighter and thinker of rights. To suspend the dependence of legal personhood on human subjectivity so that there may be bio- and artifact-rights also means to dissolve the unity between legal personality and political subjectivity that once defined the modern idea of rights. "

Abstract Treatment options for ovarian cancer patients are limited, highlighting a significant unmet need for targeted, durable, and effective therapies. In recent years, adoptive cell transfer therapies have made tremendous progress in the past years. Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are promising drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in different indications. Recently, we have reported the preclinical evaluation of a novel FOLR1-targeting CAR directed against ovarian cancer and potentially other FOLR1-expressing tumors. Despite advancements in T cell therapy, producing a functional and robust cell product in the necessary quantities remains challenging. Currently available processes for the preparation of CAR T are laborious and include numerous manual handling steps, which increase the risk of errors and may impose safety risks. This underscores the need for reliable and automated manufacturing processes to ensure high-quality cellular products for immunotherapy. This study aimed to develop an automated, closed, and good manufacturing practice (GMP)-compliant process for FOLR1-specific CAR T cells. Using the CliniMACS Prodigy® Platform, we established a streamlined process in a closed system that meets stringent regulatory requirements while reducing hands-on time. We optimized culture conditions to reduce the process time to 7 days. Starting from a cryopreserved leukapheresis we achieved a clinically relevant yield of FOLR1-specific CAR-engineered T cells. The cellular product mainly consisted of highly viable CAR-expressing T cells with an early memory phenotype. FOLR1-specific CAR T cells manufactured with the optimized process showed specific killing of ovarian cancer cells in vitro and in an ovarian cancer xenograft model in vivo. Moreover, the automated CliniMACS Prodigy Platform enables point-of-care (POC) manufacturing. In conclusion, we developed a robust, rapid, and efficient process for manufacturing anti-FOLR1 CAR T cells. This platform is well-suited for automated and decentralized POC manufacturing and can be adapted for the production of other CAR T cell therapies. Citation Format: Christoph Herbel, Manuel Martinez-Osuna, Larissa Steiner, Maria Bethke, Leon Osinski, Katrin Krischer, Janina Brauner, Cathrin Bleilevens, Jens Kopatz, Katja Petry, Dominik Eckardt. Point-of-care manufacturing of FOLR1-directed CAR T cells for the treatment of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6100.

Abstract Major advances have been achieved in targeted immunotherapy with significant clinical benefits for patients. However, on-target/off-tumor toxicity is a major concern. This issue highlights the clinical need for better targets to improve the safety profile of immunotherapies. On-target/off-tumor toxicity is mainly based on the expression of tumor-associated antigens (TAA) in healthy tissues under physiological conditions. Thus, new approaches have to be developed to restrict specificity of targeted immunotherapy selectively towards cancerous cells. One way to improve target specificity is multi-targeting of cancer cells, i.e. targeting more than one TAA per cancer cell. We developed a workflow to identify new tumor markers employing an unbiased high throughput flow cytometry-based screen on primary ovarian cancer samples. Co-expression of THY1, a marker of fibroblasts and hematopoietic stem cells, was revealed on cancer cells characterized by EPCAM expression, a marker of epithelial cells. We confirmed our findings by high content imaging analyzing several ovarian carcinoma samples. Next we assessed the safety profile of the target combination THY1-EPCAM by analyzing the expression across a multitude of healthy human tissue samples using again high content imaging. Cluster analysis showed correlation patterns within the datasets confirming our previous findings. In order to investigate the functionality of THY1-EPCAM as therapeutic t we combined this target pair with the adaptor CAR technology, a modular system composed of a CAR recognizing biotin and biotinylated antibodies which are specific for a certain antigen. This technology combines the flexibility and controllability of antibodies with the efficacy of CAR T cell-dependent killing of target cells. The functional in vitro characterization of adaptor CAR T cells targeting the THY1-EPCAM pair shows high specificity and efficacy. Moreover, we are going to conduct in vivo studies with adaptor CAR T cells to investigate the efficacy and safety of targeting THY1-EPCAM in a solid tumor model. In conclusion, we successfully identified a novel target combination in ovarian cancer utilizing flow cytometry-based screening complemented by high content imaging. The new target pair combination shows promising results in vitro in combination with adaptor CAR T cells indicating its potential use as future immunotherapy. Citation Format: Christoph Herbel, Vera Dittmer, Manuel Martinez-Osuna, Sandy Reiß, Peter Mallmann, Dominik Ratiu, Michael Mallmann, Paurush Praveen, Werner Müller, Dominik Eckardt, Andreas Bosio. Identification of a novel tumor marker combination THY1-EPCAM for adaptor CAR T cell therapy in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2813.

Abstract Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies globally with up to 50 % of patients eventually progressing to metastatic disease. The mitogen-activated-protein kinase (MAPK) pathway emerges as a key player, being one of the most frequently mutated signaling pathways in the oncogenesis of CRC. However, given the numerous genomic aberrations and tumor heterogeneity in CRC, patients may benefit from combinatorial therapies, particularly those who have inoperable or metastatic tumors. In the present study, we investigated the feasibility of combining two platforms, patient-derived 3D (PD3D®) models with Optim.AI™, to identify more effective cancer therapies. PD3D® models can robustly retain the genotypic and histopathologic features of the primary patient tumor, model tumor heterogeneity and were shown to predict a patient’s drug response. Optim.AI™ is a hybrid computational-experimental platform that uses small data sets to rationally converge to optimal drug combinations within a defined drug search space. By mapping experimental data points to a second-order quadratic function, Optim.AI™ can predict every possible 531k data points and thus the cell-killing efficacy for all other possible combinations without testing each individual drug-dose combination. Two CRC PD3D® models with different mutation profiles were tested with 155 different combinations of 12 drugs at variant concentrations. The post-treatment cell viability was measured and used for Optim.AI™ analysis to evaluate and compare the best therapies. Optim.AI™ analysis revealed differential drug sensitivity between tested CRC PD3Ds®. The top-ranked drug combinations included SN-38, active compound of commonly used chemotherapeutic irinotecan, paired with MEK-inhibitors trametinib or cobimetinib which we could confirm with both platforms. With this study, we successfully demonstrated the feasibility, the robustness, and the efficiency of combining PD3Ds® and Optim.AI™ in identifying effective drug combination therapies, here for CRC, within one month. This combined technology provides precise insights into tumor treatability and its functional causes of treatment outcomes, leading to new treatment combinations and accelerating the development of new cancer drugs in a time- and cost-effective manner. Citation Format: Ulrike Pfohl, Masturah Mohd Abdul Rashid, Jhin Jieh Lim, Juergen Loskutov, Lena Wedeken, Edward Kai-Hua Chow, Hugo Saavedra, Christoph Reinhard, Christian R. Regenbrecht. Turning data into information: Using PD3D® models to guide colorectal cancer therapy by Optim.AITM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 891.