Immunization with the CSF-470 vaccine plus BCG and RHGM-CSF induced in a cutaneous melanoma patient a TCRb repertoire found at vaccination site and tumor infiltrating lymphocytes that persisted in blood

ARIS, MARIANA; BRAVO, ALICIA INÉS; GARCIA ALVAREZ, HELI MAGALÍ; CARRI, IBEL; PODAZA, ENRIQUE; BLANCO, PAULA ALEJANDRA; ROTONDARO, CECILIA; BENTIVEGNA, SOFIA; NIELSEN, MORTEN; BARRIO, MARÍA MARCELA; MORDOH, JOSÉ

Congreso; Reunión Anual de Sociedades de Biociencias; 2019

The CSF-470 cellular vaccineplus BCG and rhGM-CSF increased distant metastases-free survival inCutaneous Melanoma (CM) patients stages IIB-IIC-III relative tomedium dose IFN-a2b (CASVAC-0401 study). Patient-045 developed amature vaccination site (VAC-SITE) and a regional cutaneousmetastasis (C-MTS) which were excised during the protocol, remainingdisease -free 36 months following vaccination. CDR3-TCRB repertoiresequencing in PBMC and tissue samples, along with skin-DTH score andIFN-G ELISPOT assay were performed to analyze the T-cell immuneresponse dynamics throughout the immunization protocol.Histopathological analysis of the VAC-SITE revealed a highly-inflamedgranulomatous structure encircled by CD11c+nested-clusters, briskCD8+ and scarce FOXP3+ lymphocytes; with numerous Langhansmultinucleated-giant-cells and macrophages. A large tumor-regressionarea fulfilled the C-MTS with brisk lymphocyte infiltration, mainlycomposed of CD8+PD1+ T-cells, CD20+ B-cells, and scarce FOXP3+ cells.Increasing DTH score and IFN-G ELISPOT assay against CSF-470vaccine-lysate was evidenced. TCRB repertoire analysis revealed forthe first time the presence of common clonotypes between a VAC-SITEand a C-MTS; most of them persisted in blood by the end of theimmunization protocol. In-vitro boost with vaccine-lysate revealedexpansion of persistent clones infiltrating the VAC-SITE and/or theC-MTS. Expansion of such persistent clonotypes might derive from twodifferent although complementary mechanisms: proliferation ofspecific clones as well as expansion of redundant clones, whichincreased the number of nucleotide rearrangements per clonotype,suggesting a functional antigenic selection. In this patient,immunization with the CSF-470 vaccine plus BCG and rhGM-CSF induced aT-cell repertoire at the VAC-SITE that was able to infiltrate anemerging C-MTS, resulting in the expansion of a T-cell repertoirewhich persisted in blood by the end of the 2 -year treatment.p { line-height: 115%; margin-bottom: 0.1in; background: transparent }