Therapeutic Vaccine CSF-470 Plus BCG Plus Rhgm-CSF for Adjuvant Treatment of High-Risk Cutaneous Melanoma Patients: Results from Phase II Study and Immune Responses

BARRIO, MARÍA MARCELA; PAMPENA, MARÍA BETINA; ARIS, MARIANA; PODAZA, ENRIQUE; CARRI, IBEL; HOLLIDAY, CARTAR; BLANCO, PAULA ALEJANDRA; BRAVO, ALICIA INÉS; VON EUW, ERIKA; NIELSEN, MORTEN; MORDOH, JOSÉ

San Francisco

Conferencia; International Conference on Immunity and Immunochemistry; 2019

United Scientific Group

The CSF-470 vaccine consists of lethally irradiated cells derived from four cutaneous melanoma cell lines established in-house, with BCG and GM-CSF as adjuvants. In a phase II clinical trial vs IFN-α2b, the vaccine significantly prolonged the distant metastasis-free survival of high-risk patients with good quality of life. Immune response against the vaccine cells was measured by DTH and IFN-γ ELISPOT. Applying whole-exome sequencing, neoantigen prediction (MuPexi), RNASeq and TCRβ sequencing we analyzed the immune response induced by CSF-470 vaccination. Vaccinated patient`s PBMC recognized patient`s HLA-restricted class I and class II peptides from non-mutated tumor associated antigens (TAA), present in the vaccine. In patient #006, INF-γ response against 9 predicted neoantigens was evidenced and 7/9 neoAgs were recognized only after vaccination. For patient #006, changes in TCRβ clonotypes in peripheral immune populations as well as in the tumor compartment suggest that CSF-470 induces an antitumor adaptive immune repertoire that can reach cutaneous metastasis (C-MTS) and persists in blood for at least 2-yrs. Also, in patient #045, TCRβ clonotypes expanded from a vaccination site (VAC-SITE) and were able to infiltrate a C-MTS. Interestingly, we found that VAC-SITE and C-MTS presented TCRβ clonotypes with high specific redundancy, with even >20 TCR clones with different nucleotide sequences converging to the same amino-acidic sequence. These results support the hypothesis that biologically relevant T-cell clones might expand through proliferation of several redundant TCR clones, underlying a functional selection.