Adam D Cohen

..This review discusses the role of GITR as a potential target for immunomodulatory therapy, as well as the research involved in understanding the mechanisms of anti-GITR therapy and current progress in translation into the clinic...

..Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients...

..Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves...

..These findings provide further support for the continued development of agonist anti-GITR mAbs as an immunotherapeutic strategy for cancer...

..These results demonstrate that DNA immunization against tissue-restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor effects without causing GVHD...

..Immune modulation, such as inducing GITR signaling, is required to enhance CD8(+) T-cell responses to specific mutations and to lead to tumor rejection...

..Together, these data indicate that lack of anti-tumor efficacy is not solely due to ignorance of self antigen in the tumor microenvironment but rather to active immunosuppressive influences preventing a protective immune response...

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..It gives a brief history and then discusses the proposed mechanism of action, preclinical and clinical studies, and methods of enhancing the immune responses induced by DNA vaccines...

..Closer examination revealed that diminished intratumoral T reg cell levels resulted from hyperactivation and T reg cell-specific apoptosis. Thus, we propose that CTX and OX40 engagement represents a novel and rational chemoimmunotherapy...

..Gaining greater mechanistic understanding of the effects of anti-GITR antibody on tumor immunity will allow for more rational translation of this promising immunotherapeutic approach to the clinic. ..