Melanoma
Conditions
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.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
: * Patients aged18-years old or over * ECOG score between 0-2 * Inoperable stage III or stage IV melanoma * Naïve of treatment or in progression after one or several treatment lines * Give their written consent for the present study and be included in MelBase cohort. * health insurance coverage. Supplementary inclusion criteria for part II : * skin or subcutaneous melanoma lesions * agree and inform consent for a cutaneous biopsy or a tumor sample if presenting lymph nodes involvement if part of the usual clinical practice.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | at 1 year | — |
| Objective response rate | at one year | — |
| Overall survival | at 1 year post inclusion | — |
| 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 | — |
| 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 |
Contacts
Primary ContactCeleste Lebbe, Pr
Backup ContactMatthieu Resche-Rigon, Pr
Outcome results
None listed