Test of CD47-SIRPα Inhibitors on the Immune Microenvironment Colon Cancer

Study Overview
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Brief Summary
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Our goal is to create novel CD47-SIRPα inhibitors using small molecules to reverse TAM-mediated immune suppression and restore anti-tumor immunity in CRCs. Our program uses structure-based drug design to create selective and potent small molecule inhibitors of SIRPα-CD47 to target the tumor microenvironment with greater efficacy and lower toxicity than CD47-targeting antibodies. . In order to study the activity of CD47-SIRPα inhibitors on the immune microenvironment of tumors, we propose to use organoids derived from biopsies of patients with colon cancer. Tumoroids preserve the patient's tumor stroma (including myeloid cells) and provide an accurate in vitro model of complex tumor immune interaction for the evaluation of immunotherapies.

Official Title
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Test of CD47-SIRPα Inhibitors on the Immune Microenvironment Colon Cancer

Conditions
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Cancer of the Colon

Intervention / Treatment
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* Procedure: BLOOD AND TUMOR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient over 18 years old Patient who has signed a consent to participate; Patient with metastatic or non-metastatic colon cancer, or recurrence of colon cancer for whom excision surgery has been proposed; Patient affiliated to a social security scheme, or beneficiary of such a scheme Exclusion Criteria: Patient who had emergency colon cancer surgery Person in an emergency situation or unable to express their consent. Adult subject to a legal protection measure (adult under guardianship, curatorship or safeguard of justice), Patient unable to submit to the medical follow-up of the trial for geographical, social or psychological reasons

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

| Intervention/Treatment |
| --- |
|Procedure: BLOOD AND TUMOR|sampling of 24 ml of peripheral blood and samples of colon cancers with healthy tissue in parallel on the surgery piece|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of patient derived organoids (minimum n=30) resembling the primary tissue sample | the capacity to establish patient-derived organoids from tumor and adjacent normal tissue will be evaluated using a histology score evaluating and comparing primary and organoid sample characteristics. | 18 months from study launch | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of a validated cryobank of patient derived organoids (minimum n=30) | the capacity to establish a cryobank of patient-derived organoids from tumor and adjacent normal tissue will be evaluated using a growth score evaluating and comparing organoid sample characteristics pre- and post-cryopreservation and amplification through 4 passages. | 18 months from study launch | 
| Generate a T cell biobank by FACS isolating T cells using the CD3 surface marker directed against the human form |  | 48 month | 
| To assess the effect of immunotherapy on the antitumor activity of autologous T cells from peripheral blood samples using tumor viability measurements (cell titer glo, FACS) |  | 48 month |