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Research Articles: Therapeutics, Targets, and Development

A chaperone protein-enriched tumor cell lysate vaccine generates protective humoral immunity in a mouse breast cancer model

¹ Department of Pediatrics, University of Arizona, Tucson, Arizona and ² Division of Surgical Oncology, Department of Surgery, ³ Departments Microbiology, Immunology and Molecular Genetics, and ⁴ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California

Requests for reprints: Emmanuel Katsanis, Department of Pediatrics, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724. Phone: 520-626-4851; Fax: 520-626-6986. E-mail: katsanis{at}peds.arizona.edu

Abstract

We have documented previously that a multiple chaperone protein vaccine termed chaperone-rich cell lysate (CRCL) promotes tumor-specific T-cell responses leading to cancer regression in several mouse tumor models. We report here that CRCL vaccine generated from a mouse breast cancer (TUBO, HER2/neu positive) is also capable of eliciting humoral immunity. Administration of TUBO CRCL triggered anti-HER2/neu antibody production and delayed the progression of established tumors. This antitumor activity can be transferred through the serum isolated from TUBO CRCL-immunized animals and involved both B cells and CD4⁺ T lymphocytes. Further evaluation of the mechanisms underlying TUBO CRCL-mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results suggest that tumor-derived CRCL vaccine has a wider applicability as a cancer vaccine because it can target both T-cell- and B-cell-specific responses and may represent a promising approach for the immunotherapy of cancer. [Mol Cancer Ther 2008;7(3):721–9]

Grant support: American Cancer Society IRG grant CA23074 (S. Andreansky); NIH grant R21 CA102410 (E. Katsanis); and Tee Up for Tots, Raise a Racquet for Kids Funds, NIH/National Cancer Institute grant CA86915 (M.L. Penichet), Cindy Corona Memorial Gift, and AACR-California Department of Health Services Career Development Award in Gender-Related Cancer Research (M.L. Penichet).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: G. Li and S. Andreansky contributed equally to this work.

Received 9/12/07; revised 11/21/07; accepted 12/14/07.