Towards optimization of the anti-melanoma vaccine CSF470

BENTIVEGNA, SOFIA; MORDOH, JOSE; CARTAR, HOLLIDAY; MADORSKY ROWDO, FLORENCIA PAULA

Tucuman

Congreso; LXVII Reunion Cientifica Anual de la Sociedad Argentina de Inmunologia; 2019

Introduction. The CSF470 vaccine is a mixture of four irradiated cell lines, with GM-CSF andBCG as adjuvants. A Phase II study in cutaneous melanoma patients comparing its efficacy andsafety against IFN-α demonstrated that CSF470 was superior in quality of life and distantmetastases-free survival. However, BCG induced a strong local reaction in a minority of patientsand its dose had to be diminished. Since BCG vaccination is not mandatory in many countries,we analyzed other adjuvants. Using patient ́s blood samples we investigated the immuneresponses towards each cell line composing CSF470.Methodology. 1) PBMC from normal donors were co-cultured in vitro with CSF470. BCG, poly(I:C) or QS-21 effect on cytokines release was examined at 6, 24 and 48 hours. 2) As only XY1,one component of CSF470, was a high producer of IL-10, the effect of its omission (CSF370) ondendritic cells (DC) maturation and ability to present MART-1 to the CD8 clone M26 wasanalyzed. DC were obtained from CD14+ blood monocytes and differentiated in vitro. Aftercharging DC with CSF470 or CSF370, their maturation and MART-1 presenting ability wereanalyzed. 3) ELISPOT assay was used to investigate the reactivity of a patient?s PBMC againstindividual cell lines composing CSF470.Results and Conclusions. In comparison to poly (I:C) or QS-21, BCG was a better adjuvant. Theabsence of IL-10 in the CSF370 vaccine did not modify the DC maturation and MART-1-presenting abilities with respect to CSF470. Vaccinated patient?s PBMC reacted differently withindividual cell lines.