Recombinant adenovirus vaccine encoding a chimeric T-cell antigen receptor induces protective immunity against a T-cell lymphoma.
Vaccination using recombinant tumor-derived T-cell antigen receptor (TCR) protein induces a protective, idiotype-specific immune response against a murine T-cell tumor. However, the technically demanding task of producing patient-specific, recombinant TCR protein restricts the translation of TCR vaccines for clinical use. We report here the development of an effective recombinant TCR adenovirus vaccine. Individual adenoviruses were constructed to encode a chimeric TCR derived from either tumor Valpha or Vbeta regions fused to xenogeneic human constant regions. Coinjection of the chimeric alpha- and the beta-TCR adenoviruses protected mice against tumors. The level of protection was comparable to that achieved by an optimized regimen of recombinant TCR protein vaccines. Tumor immunity induced by TCR adenoviruses required the xenogeneic constant regions and was mediated by CD8+ T cells. Independent vaccines consisting of adenovirus expressing either chimeric alpha- or beta-TCR chain also stimulated a protective immune response. Immunization with TCR adenovirus may offer a new efficacious, protein-free vaccination approach for the treatment of T-cell malignancies.
Wong
C P
CP
Division of Oncology, Stanford University Medical Center, California 94305, USA.
Levy
R
R
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000912:Antibodies, Neoplasm; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines