Idiotype vaccination strategies against a murine B-cell lymphoma: dendritic cells loaded with idiotype and bispecific idiotype x anti-class II antibodies can protect against tumor growth.

Abstract

Three strategies were used to evaluate 38C13 B-cell lymphoma-specific idiotype immunization to protect against subsequent lymphoma challenge in C3H/He mice. It was observed that tumor-specific immunity could be induced by immunization with (i) KLH-conjugated 38C13 B-cell lymphoma idiotype in complete Freund's adjuvants (survival rate 80%), (ii) dendritic cells pulsed in vitro with native idiotype protein (survival rate 80%), and (iii) bispecific antibodies composed of B-lymphoma-related idiotype and an MHC class II binding moiety (survival rate 40%). Presentation of idiotype determinants by dendritic cells or bispecific antibody resulted in lymphoma-specific immunity and obviated the requirement for carrier protein or adjuvant. Moreover, primed dendritic cells induced predominant development of a tumor-specific T-cell response. Each of these immunization strategies resulted in long-term survival without the emergence of idiotype variants or the induction of tumor dormancy.