Clinical trial NCT02880046: Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies
Official title: Study of Polyfunctionality of Anti-tumor T Lymphocytes in Cancerology: Potential Biomarker for Emerging Immunotherapies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer
Keywords: immune response
T lymphocyte
PD-1/PDL-1 pathway
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-08-26
Enrollment: 90
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Frozen samples from patients affected by melanoma (LyteloMel), lung cancer (TeloCap) or renal carcinoma (EMIR) from cohorts of medical oncology department of CHRU Besançon (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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: 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
timeFrame: Inclusion
Secondary outcomes:
measure: Polyfunctionality of UCP and/or survivin-specific responses of T lymphocytes in each cohort
timeFrame: Inclusion
measure: Amplitude of UCP and/or survivin-specific responses of T lymphocytes in presence of anti-PDL-1 antibody or isotype control
timeFrame: Inclusion
measure: Amplitude of UCP and/or survivin-specific responses of T lymphocytes evaluated with flow cytometry or IFN-γ Elispot assay
timeFrame: Inclusion
Other outcomes:
Locations:
Study officials:
affiliation: Laboratoire d'immunologie - CHRU Nancy
name: Marcelo DE CARVALHO BITTENCOURT, Pr
role: PRINCIPAL_INVESTIGATOR
References: