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A Novel Human Cancer Vaccine Elicits Cellular Responses to the Tumor-Associated Antigen, Human Chorionic Gonadotropin ß

¹ Medarex, Inc., Bloomsbury, New Jersey, and ² Dartmouth Medical School, Lebanon, New Hampshire

ABSTRACT

Purpose: The oncofetal antigen, human chorionic gonadotropin ß subunit (hCGß), is expressed by a number of carcinomas and is a prognostic indicator in renal, colorectal, bladder, and pancreatic cancers. We describe the development of a novel antibody-based dendritic cell (DC)-targeted cancer vaccine capable of eliciting cellular immune responses directed against hCGß.

Experimental Design: The tumor-associated antigen hCGß was coupled genetically to a human anti-DC antibody (B11). The resulting fusion protein (B11-hCGß) was evaluated for its ability to promote tumor antigen-specific cellular immune responses in a human in vitro model. Monocyte-derived human DCs from normal donors were exposed to purified B11-hCGß, activated with CD40 ligand, mixed with autologous lymphocytes, and tested for their ability to promote hCGß-specific proliferative and cytotoxic T-lymphocyte responses.

Results: B11-hCGß was found to be a soluble, well-defined, and readily purified product that specifically recognized the human mannose receptor via the B11 antibody portion of the fusion protein. B11-hCGß functionally promoted the uptake and processing of tumor antigen by DCs, which led to the generation of tumor-specific HLA class I and class II-restricted T-cell responses, including CTLs capable of killing human cancer cell lines expressing hCGß.

Conclusions: Although other hCG vaccines have been shown to be capable of eliciting antibody responses to hCGß, this is the first time that cellular immune responses to hCGß have been induced by a vaccine in a human system. This DC-targeted hCGß vaccine holds promise for the management of a number of cancers and merits additional clinical development.

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