Assesment of T cell response induced in cutaneous melanoma patients treated with the CSF-470 therapeutic vaccine in the adjuvant setting

PODAZA, ENRIQUE; CARRI, IBEL; ARIS, MARIANA; BLANCO, PAULA; NIELSEN, MORTEN; MORDOH, JOSÉ; BARRIO, MARÍA MARCELA

San Miguel de Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

The CSF-470 vaccine consists of allogeneic lethally-irradiated cells from four cutaneous melanoma cell lines administered plus BCG and GM-CSF as adjuvants. In a phase II study the vaccine significantly prolonged the distant metastasis-free survival of high-risk melanoma patients. Since DTH and IFN-γ ELISPOT against the vaccine cells evidenced patient’s T-cell responses, our aim was to analyze the nature of the Ags recognized by T cells. We focused on shared non-mutated tumor-associated antigens (TAAs) expressed in vaccine cells and on mutated patient-specific neoantigens (neoAgs). Haplotype was determined for evaluable patients (n= 13), and HLA restricted TAAs- derived peptides were selected from the TANTIGEN database. Also, somatic mutations were obtained from paired tumor:PBMC (pt#006) by whole exome sequencing; candidate neoAgs were predicted using MuPexi. PBMC´s response to synthetic peptides was assessed by INF-γ ELISPOT. Additionally, lytic capacity and CD4+ helper profile of patient´s PBMCs were evaluated. We evidenced a powerful and progressively increasing immune response against shared TAAs after CSF-470 vaccination in all patients. In pt#006, this response also targeted several predicted neoAgs (not expressed in CSF-470), whose exposure and consequent recognition by the immune system increased after vaccination. Furthermore, lytic clones were evident after in vitro stimulation with the vaccine lysate and helper response analyzed ex vivo was mainly Th1.