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An Effective Vaccine Strategy Protective against Antigenically Distinct Tumor Variants

Department of Immunology, College of Medicine, Mayo Clinic, Rochester, Minnesota

Requests for reprints: Larry R. Pease, Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-284-8177; Fax: 507-266-0981; E-mail: pease.larry{at}mayo.edu.

Key Words: CTL • B7-DC XAb • immunotherapy

Antigenically distinct tumor variants can emerge in response to selective pressures inherent to host-tumor interactions. The development of successful immunotherapeutic strategies can be limited by these disparate antigenic profiles. Using the immunomodulator B7-DC XAb to activate cytolytic T cells specific for tumor-associated antigens, we found that the specificity of immune responses elicited by live tumors are distinct from the specificity of the responses elicited by soluble proteins derived from the same tumors. Remarkably, whereas the induced antitumor immunity generated against live variants of the B16 melanoma and EL4 thymic lymphoma tumors were highly specific for the original tumor variant used in the challenge, immunity generated using soluble proteins derived from tumor lysates was broadly reactive, recognizing the challenge tumor, as well as antigenically distinct variants. The antigens detected using live tumor and tumor lysate vaccines could be distinguished biochemically, demonstrating that they are structurally distinct. We show that vaccines using antigens present in tumor cell lysates induce protective immunity with strong memory against distantly related tumor variants. The existence of a class of antigens shared among tumor variants provides an attractive target for vaccine development. [Cancer Res 2008;68(7):2471–8]