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


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 ?Gal-specific antibodies, the most abundant naturally occurring antibodies in human serum, inhibits tumor growth in mice treated with a VEGF aptamer-?Gal hapten conjugate, and recruits antibodies from human serum to human tumor biopsies of distinct origin. Thus, treatment with ?Gal hapten conjugated to broad-spectrum tumor targeting ligands could enhance the susceptibility of a broad range of tumors to immune elimination.

SUBMITTER: Schrand B 

PROVIDER: S-EPMC6105580 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Schrand Brett B   Clark Emily E   Levay Agata A   Capote Ailem Rabasa AR   Martinez Olivier O   Brenneman Randall R   Castro Iris I   Gilboa Eli E  

Nature communications 20180822 1


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  ...[more]

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