Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 90
- Primary Endpoint
- Polyfunctionality of universal cancer peptides (UCP) and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control, evaluated with flow cytometry
Study Overview
Brief Summary
Purposes of this study are :
- Characterization of polyfunctionality of anti-tumor T lymphocytes using in vitro inhibition of PD-1/PDL-1 pathway
- Study and comparison of polyfunctionality of anti-tumor T lymphocytes in cohorts of patients with melanoma, lung cancer and renal carcinoma. This cancers are chosen because of use of anti-PD-1 or anti-PDL-1 antibodies
- Comparison of this technique with IFN-γ Elispot assay for detection and quantification of anti-tumor T lymphocytes after in vitro blockade of PD-1/PDL-1 pathway.
Detailed Description
In this study an immunomonitoring of specific responses of T lymphocytes to tumor-associated antigens based on detection of intracellular cytokines through flow cytometry, after stimulation with all-tumor antigens and blockade of PD-1/PDL-1 interaction is used. Peripheral blood mononuclear cells of patients with cancers are stimulated with 4 telomerase-peptides or peptides overlapping the entire sequence of survivin.
This project studies the frequency and role of polyfunctionality of anti-tumor T lymphocytes in cancerology with an in vitro technique detecting polyfunctional T lymphocytes with a better sensitivity based on removal of an inhibitory PD-1/PDL-1 pathway. It is a flow cytometry protocol with various theoretical advantages in terms of reproducibility and dynamic monitoring of functionality of different sub-populations of polyfunctional anti-tumor T lymphocytes. Moreover, it allows the study of molecular mechanisms involved in proliferation of polyfunctional anti-tumor T lymphocytes with the possibility to sort sub-populations.
The use of all-tumor antigens allows the use of this technique to evaluate the presence and prognostic or predictive value of this biomarker in various cancers.
Detection of polyfunctional anti-tumor T lymphocytes can be a biomarker of anti-tumor lymphocytic adaptive immunity and a potential eligibility or efficacy criteria for new immunotherapies, such as anti-PD-1 or anti-PDL-1 treatments.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients affected by melanoma (LyteloMel), lung cancer (TeloCap) or renal carcinoma (EMIR) from cohorts of medical oncology department of CHRU Besançon (France)
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Polyfunctionality of universal cancer peptides (UCP) and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control, evaluated with flow cytometry
Time Frame: Inclusion
Secondary Outcomes
- Amplitude of UCP and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control(Inclusion)
- Amplitude of UCP and/or survivin-specific responses of T lymphocytes evaluated with flow cytometry or IFN-γ Elispot assay(Inclusion)
- Polyfunctionality of UCP and/or survivin-specific responses of T lymphocytes in each cohort(Inclusion)