Immunological responses promoted by therapeutic CSF-470 vaccine plus adjuvants in cutaneous melanoma patients: conclusions of a phase II clinical trial

PAMPENA, MARÍA BETINA; BLANCO, PAULA ALEJANDRA; BARRIO, MARÍA MARCELA; LEVY, ESTRELLA MARIEL; MORDOH, JOSÉ

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Cutaneous melanoma (CM) incidence is increasing veryfast and, given its aggressiveness, once it has metastasized treatmentoptions are limited and the prognosis is bleak. We presenthere the inmune monitoring results of Phase II part of CASVAC-0401study. 30 post-surgery CM patients (pts) stages II/III were randomizedto receive CSF-470 vaccine (n=19) or IFN-α2b (n=11) during 2years. CSF-470 vaccine is a mini-allograft consisting of 4 lethally-irradiatedallogeneic CM cell lines, combined with BCG and GM-CSFas adjuvants. With a mean and a maximum follow-up of 36.1 and 90months respectively, higher distant metastasis-free survival for CSF-470 treated pts was observed (p=0.02, G-B-Wilcoxon Test). Giventhat all vaccinated pts developed inflammation at the vaccinationsite and an increment in DTH response, we evaluated the immunechanges promoted by CSF-470 vaccine and IFN-α2b in PRE andPOST1 (6 months, 5 vaccinations) peripheral blood (PB) samples.Immune monitoring showed an increase in antitumoral cellularand humoral responses. Although vaccinated pts did not increaseT CD4+ and CD8+ cells, a significant augmentation in NK cell frequencyin the POST1 sample was observed (PRE 16.4±7.6% vsPOST1 21±11.8% p=0.01, paired T test). Phenotypic and functionalassays showed functional competence of these cells. To determinePB T cells reactivity to CM antigens, IFN-γ ELISPOT assay was performedafter stimulation with vaccine lysate. A significant increasein specific T cells against CM antigens was detected in POST1samples of 14/15 pts (PRE 65,4±80.6 spots vs POST1 220.2±97.2spots, p=0.0001, paired T test). Besides, we observed a significantincrease in antibody response against CM cells in vaccinated ptssera (ELISA assay, 1/10 dilution, PRE 0.3±0.2 vs POST1 0.8±0.3;p