Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies

• Conditions: Cancer

• Registration Number: NCT02880046
• Lead Sponsor: Central Hospital, Nancy, France

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 Timeline

• Status Verified: 2016-08
• Study First Submitted: 2016-08-23
• Study First Submitted QC: 2016-08-25
• Last Update Submitted: 2016-08-25
• Study First Posted: 2016-08-26
• Last Update Posted: 2016-08-26
• Study Start: 2016-10
• Primary Completion: 2017-10
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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	Inclusion

Secondary Outcome Measures

Name	Time	Method
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