Synta Announces Journal Publication Describing Complementary Activity of Hsp90 Inhibition and Immune Checkpoint Blockade for Cancer Therapy
The review article describes preclinical findings that suggest that proteasomal degradation of cellular client proteins associated with Hsp90 inhibition may augment antitumor immune response through increased cellular antigen expression and subsequent enhanced T-cell recruitment and tumor-cell recognition. The review article also explains that client proteins affected by Hsp90 inhibition include oncogenes that may drive expression of Programmed Death-Ligand 1 (PD-L1), a key immune checkpoint. The resulting reduction of PD-L1 expression on tumor cells may increase T-cell mediated cytotoxic activity and complement the activity of selective anti-PD-1 or anti-PD-L1 antibody therapies. This is supported by in vivo study results, where ganetespib was found to potentiate the antitumor efficacy of anti-PD-L1 antibody treatment. In these studies, the combination of ganetespib and an anti-PD-L1 antibody displayed significantly greater antitumor activity than either individual agent, in mouse models of both colon carcinoma and melanoma.
“While there is still more to learn regarding the mechanistic basis for
combining Hsp90 and immune checkpoint inhibitors, and the role of Hsp90
in antitumor immunity, the findings in this review suggest that this
approach may be complementary and therapeutically advantageous. We look
forward to exploring the combination of immune checkpoint inhibitors and
ganetespib in future clinical studies,” said
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is an innovative, agile biopharmaceutical company focused on research, development and commercialization of novel oncology medicines that have the potential to change the lives of cancer patients. Synta’s lead oncology drug candidate, ganetespib, a novel heat shock protein 90 (Hsp90) inhibitor, is currently being evaluated in several clinical trials including the pivotal GALAXY-2 Phase 3 trial in non-small cell lung cancer. Building on its extensive expertise in the science of Hsp90, Synta also has a novel proprietary Hsp90 inhibitor Drug Conjugate (HDC) small molecule drug development program. IND enabling studies have commenced for the first clinical candidate from the HDC program, STA-12-8666, and preclinical evaluation of additional HDC candidates is ongoing. For more information, please visit www.syntapharma.com.
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