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Experimental Therapeutics |
Division of Oncology, Stanford University Medical Center, Stanford, California 94305
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 V
or Vß regions fused to xenogeneic
human constant regions. Coinjection of the chimeric
- and the
ß-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
- or ß-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.
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