Recombinant adenovirus vaccine encoding a chimeric T-cell antigen receptorinduces protective immunity against a T-cell lymphoma

Vaccination using recombinant tumor-derived T-cell antigen receptor (TCR) p rotein induces a protective, idiotype-specific immune response against a mu rine T-cell tumor, However, the technically demanding task of producing pat ient-specific, recombinant TCR protein restricts the translation of TCR vac cines for clinical use, We report here the development of an effective reco mbinant TCR adenovirus vaccine. Individual adenoviruses were constructed to encode a chimeric TCR derived from either tumor V alpha or V beta regions fused to xenogeneic human constant regions. Coinjection of the chimeric alp ha- and the beta-TCR adenoviruses protected mice against tumors. The level of protection was comparable to that achieved by an optimized regimen of re combinant TCR protein vaccines. Turner immunity induced by TCR adenoviruses required the xenogeneic constant regions and was mediated by CD8(+) T cell s, Independent vaccines consisting of adenovirus expressing either chimeric alpha- or beta-TCR chain also stimulated a protective immune response, Imm unization with TCR adenovirus may offer a new efficacious, protein-free vac cination approach for the treatment of T-cell malignancies.