Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?

Not yet recruiting

• Conditions: Melanoma

• Registration Number: NCT04477876
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Although immunotherapy revolutionized melanoma outcomes over the last 10 years, only 40-50% of patients respond to treatments and 25% develop acquired resistances. Natural Killer (NK) cells naturally recognize and kill tumor cells. However, the immunosuppressive micro-environment generated by the tumor decreases NK cells' killing activity. CD160 is a NK cell receptor identified and characterized in our laboratory. Engagement of the GPI isoform (CD160-GPI) initiates NK cell cytotoxic response. Upon NK cell activation, a transmembrane isoform (CD160-TM) is neo-synthesized which promotes the amplification of activated NK cell cytotoxicity.

The aim of this study is to assess the phenotypic profile of advanced stages melanoma patients' NK cells (mainly CD160-TM expression or its induction) and therefore the therapeutic potential of the use of an anti-CD160-TM agonist antibody to boost the NK-dependent mechanism leading to tumor depletion.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-02
• Study First Submitted: 2020-05-11
• Study First Submitted QC: 2020-07-17
• Last Update Submitted: 2020-07-17
• Study First Posted: 2020-07-20
• Last Update Posted: 2020-07-20
• Study Start: 2020-09-01
• Primary Completion: 2027-12-15
• Study Completion: 2027-12-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

• Pregnant and breastfeeding women
• Patients with psychiatric disorders
• Patients already included in another clinical trial
• Having received chemotherapy or radiotherapy during the last 4 weeks,
• Patient presenting another solid or blood cancer, chronic viral infection (e.g. HIV, HBV or HCV)
• Been treated with more than 10mg of steroids until the 4 weeks before inclusion.
• Refusal to participate to the study
• Patients under guardianship or curatorship
• Patients on state medical aid

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of effector cells activation and degranulation (CD69 and CD107a staining )	at inclusion	Difference between cells incubated with the anti CD160-TM antibody and with isotipic control ab ( flow cytometry)

Secondary Outcome Measures

Name	Time	Method
Overall survival	at 5 years post inclusion
Progression free survival	at 5 years
Objective response rate	at 5 years
Phenotypic characteristics of NK cells	at inclusion	Assessment by flow cytometry of the expression levels of activating or inhibitory receptors (e.g. CD160-GPI, NKp46), phenotypic markers (e.g CD16, CD3), as well as activation (CD69) and degranulation (CD107a) markers by the NK cell population (defined as CD3- CD56+ cell). Results will be expressed as the % of positive cells for each marker among the NK cell population
cytokine profile	at inclusion	Assessment by flow cytometry using a cytokine beads array (BD Biosciences) of the Th1/Th2/Th17 cytokine content. The presence of the following cytokine will be assessed: IL17-A, IFN-g, TNF, IL10, IL-6, IL-4 and IL-2. The mean fluorescence intensities will be recorded and quantifications will be done, using an individual standard curve, for each cytokine. Results will be expressed in pg/ml.
Détection and quantification of sCD160 in patients' serum	at inclusion