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Comparison of Humoral Immune Responses and Tumor Immunity in Mice Immunized with Recombinant SV40 Large Tumor Antigen and a Monoclonal Anti-Idiotype¹

Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228-0147 [M. H. S., R. K. B., R. C. K.], and Department of Microbiology, The University of Texas Health Science Center, San Antonio, Texas 78284

² To whom requests for reprints should be addressed, at Department of Virology and Immunology, Southwest Foundation for Biomedical Research, P. O. Box 28147, San Antonio, TX 78228-1410.

We compared the humoral immune responses induced in BALB/c mice by immunization with recombinant SV40 large tumor antigen (T-ag) with those induced by a monoclonal anti-idiotype (anti-Id), designated 58D, that is specific for SV40 T-ag-induced Id network components. We also challenged immunized mice with a lethal dose of SV40-transformed cells to assess in vivo tumor immunity. Two biweekly immunizations with either SV40 T-ag or anti-Id 58D induced humoral responses that recognized both SV40 T-ag and anti-Id 58D. Four biweekly immunizations with SV40 T-ag increased the antigen-specific antibody titers and decreased the response to anti-Id 58D, while four biweekly immunizations of anti-Id 58D increased antibody titers to both itself and SV40 T-ag. Comparison of specific T-ag epitope and idiotope specificities indicated that SV40 T-ag and anti-Id 58D immunization generated responses that recognized a similar epitope on SV40 T-ag and expressed a shared idiotope recognized by anti-Id 58D. SV40 T-ag immunized mice challenged with a lethal dose of SV40-transformed cells were completely protected and no tumors were observed. This is despite the fact that little or no SV40 T-ag-specific cytotoxic T-lymphocyte activity was detectable. In contrast, only 3 of 10 mice immunized with anti-Id 58D were protected from a lethal challenge. These results indicate that, although monoclonal anti-Id immunization can induce responses that recognize similar SV40 T-ag epitopes and express shared idiotopes associated with antibodies to SV40 T-ag, the recombinant antigen itself induces superior in vivo tumor immunity.

¹ This study was supported by Grant IM 69051 from the American Cancer Society.

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.

Received 5/ 5/93. Accepted 9/30/93.

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