期刊
ONCOIMMUNOLOGY
卷 9, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2020.1721810
关键词
Abscopal response; bone metastases; damage-associated molecular patterns; immunotherapy; prostate cancer; avelumab; multiple myeloma
资金
- Breakthrough Level 2 grant from the US Department of Defense (DoD), Breast Cancer Research Program (BRCP) [BC180476P1]
- 2019 Laura Ziskin Prize in Translational Research from the Stand Up to Cancer (SU2C) [ZP-6177]
- Mantle Cell Lymphoma Research Initiative (MCL-RI) grant from the Leukemia and Lymphoma Society (LLS)
- Dept. of Radiation Oncology at Weill Cornell Medicine
- Rapid Response Grant from the Functional Genomics Initiative
- Lytix
- Phosplatin
PT-112 is a novel platinum-pyrophosphate conjugate under clinical development for cancer therapy. PT-112 mediates cytostatic and cytotoxic effects against a variety of human and mouse cancer cell lines in vitro. The cytotoxic response to PT-112 is associated with the emission of danger signals underpinning the initiation of anticancer immunity, including calreticulin exposure on the surface of dying cells, as well as ATP and HMGB1 secretion. Consistently, mouse cancer cells succumbing to PT-112 in vitro can be used to provide syngeneic, immunocompetent mice with immunological protection against a subsequent challenge with living tumor cells of the same type. Moreover, PT-112 administration synergizes with PD-1 or PD-L1 blockade in the control of mouse cancers in immunologically competent settings, as it simultaneously recruits immune effector cells and depletes immunosuppressive cells in the tumor microenvironment. Finally, PT-112 employed intratumorally in the context of immune checkpoint inhibition initiates a robust immune response that has systemic outreach and limits the growth of untreated, distant lesions. Thus, PT-112 induces the immunogenic demise of cancer cells, and hence stands out as a promising combinatorial partner of immune checkpoint blockers, especially for the treatment of otherwise immunologically cold tumors.
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