Creating an Innovative AI-based Technology TCRact for Designing and Optimizing T-cell Receptors (TCR) for Use in Cancer Immunotherapies

Study Overview
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Brief Summary
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The PROJECT OBJECTIVE is to create an innovative AI-based (Artificial Intelligence) IN SILICO TECHNOLOGY for the design and optimization of T-cell receptors (TCRs) capable of recognizing specific tumor antigens presented on Human Leukocyte Antigen (HLA). The technology will be based on bioinformatics (including molecular modelling) and artificial intelligence (including predictive, generative and optimization models). PROJECT TASKS are dedicated to the implementation of individual technological components (including the database necessary for their preparation) and to performing IN VITRO evaluation rounds to optimize the technology. Integration, within an IN SILICO TECHNOLOGY, of processes which currently require huge amounts of in vitro laboratory experiments that are necessary for bringing new TCR-based cancer immunotherapies into clinical trials: finding appropriate TCRs targeting cancer neoantigen presented on a HLA molecule (pHLA) testing for potential TCR toxicity (targeting self antigens presented on healthy tissues) optimization of pHLA:TCR binding affinity and toxicity.

Official Title
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Creating an Innovative AI-based (Artificial Intelligence) IN SILICO TECHNOLOGY TCRact to Launch a NEW SERVICE for Designing and Optimizing T-cell Receptors (TCR) for Use in Cancer Immunotherapies

Conditions
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Colon Cancer, Cancer

Intervention / Treatment
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* Other: Collection of blood (PBMC), biopsy (FFPE) and stool samples.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of advanced resectable colorectal cancer (Active stage III or IV) Histopathologically confirmed as adenocarcinoma Age 18 or over Being able to understand and sign the Informed Consent Form (ICF) Qualification for resection within 3 months from W0 or condition after primary tumor resection, not longer than 5 years from surgery Exclusion Criteria: Mucinous colorectal adenocarcinoma Canal and anal edge cancer, Adenocarcinoma of the appendix, Patients treated with neoadjuvant therapy or radiation therapy in the 3 months prior to study enrollment. Patients treated with systemic chemotherapy in the 3 months prior to study enrollment. Histopathological diagnosis other than adenocarcinoma Remission History of inflammatory bowel diseases Pregnancy HIV infection Active infection with hepatitis B and C viruses Leukocytopenia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COLON CANCER<br>This cohort will consist of 100 patients with Colon Cancer. | Other: Collection of blood (PBMC), biopsy (FFPE) and stool samples.<br>* Patients receiving routine treatment financed by the Polish National Health Fund (NFZ).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Finding appropriate TCRs targeting cancer neoantigen presented on a HLA molecule (pHLA) |  | Inclusion | 
| Testing for potential TCR toxicity (targeting self antigens presented on healthy tissues) |  | Inclusion | 
| Optimization of pHLA:TCR binding affinity and toxicity |  | Inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunology, TCR, FFPE, PBMC, Colon Cancer, Immuno-Oncology, Cancer, Oncology