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.

Inclusion Criteria:

• Clinical diagnosis of advanced resectable colorectal cancer (Active stage II, 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

Patients receiving routine treatment.