Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity.

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Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity.

Nat Commun. 2018 Aug 22;9(1):3348

Authors: Schrand B, Clark E, Levay A, Capote AR, Martinez O, Brenneman R, Castro I, Gilboa E

Abstract
Uptake of tumor antigens by tumor-infiltrating dendritic cells is limiting step in the induction of tumor immunity, which can be mediated through Fc receptor (FcR) triggering by antibody-coated tumor cells. Here we describe an approach to potentiate tumor immunity whereby hapten-specific polyclonal antibodies are recruited to tumors by coating tumor cells with the hapten. Vaccination of mice against dinitrophenol (DNP) followed by systemic administration of DNP targeted to tumors by conjugation to a VEGF or osteopontin aptamer elicits potent FcR dependent, T cell mediated, antitumor immunity. Recruitment of αGal-specific antibodies, the most abundant naturally occurring antibodies in human serum, inhibits tumor growth in mice treated with a VEGF aptamer-αGal hapten conjugate, and recruits antibodies from human serum to human tumor biopsies of distinct origin. Thus, treatment with αGal hapten conjugated to broad-spectrum tumor targeting ligands could enhance the susceptibility of a broad range of tumors to immune elimination.

PMID: 30135425 [PubMed - in process]

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