PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • February 11, 2020

Research

keywords

  • Antineoplastic Agents
  • Neoplasms

Identity

PubMed Central ID

  • PMC7028345

Scopus Document Identifier

  • 85079366507

Digital Object Identifier (DOI)

  • 10.1111/bph.14889

PubMed ID

  • 32117585

Additional Document Info

volume

  • 9

issue

  • 1