Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent @entity35 XXXX model.

@entity5 @entity11264 @entity3 @entity35 @entity694
BACKGROUND: CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established @entity5 and, above all, if they delay or prevent the development of distant @entity3 after RIT, using an immunocompetent syngeneic @entity35 @entity694 model. METHODS: The cytotoxic T cells were depleted in 15 rats by anti-CD8 before the injection of the radioimmunoconjugate (400  MBq/kg body weight (177)Lu-BR96, which binds to the @entity5 -associated antigen Lewis Y). Fifteen other @entity35 were treated with RIT only. Both groups were followed for 99  days. Blood samples were collected at least once weekly, and @entity5 were monitored twice weekly. RESULTS: Twenty-nine of the 30 animals exhibited local complete response. The non-responder was treated with anti-CD8 and RIT but succumbed later due to @entity3 . Five animals in the group given anti-CD8   +   RIT were sacrificed due to @entity3 , and 4 additional animals were found to have @entity3 at autopsy. In the group given RIT, 4 animals developed @entity3 , but no @entity3 were found in the remaining 11 animals at autopsy. Thus, at the end of the study, 6 animals in the anti-CD8   +   RIT group were free from @entity3 , while 11 were free from @entity3 in the group receiving RIT. CD3(+) @entity11264 (-)CD8(+) lymphocytes were consistently depleted by the anti-CD8 treatment. The myelosuppression was otherwise similar in the two groups. The initial depletion of CD8-positive cells in our syngeneic @entity35 @entity694 model resulted in a higher frequency of animals developing @entity3 . CONCLUSIONS: Depletion of CD8-positive cells during RIT in an immunocompetent @entity35 @entity5 model might influence the number of animals developing @entity3 , indicating that the immune system may be important in the long-term outcome of RIT.
