LTX-315-enabled, radiotherapy-boosted immunotherapeutic control of breast cancer by NK cells. Academic Article uri icon

Overview

abstract

  • LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumor-targeting immune responses. Here, we investigated the therapeutic activity and immunological correlates of intratumoral LTX-315 administration in three syngeneic mouse models of breast carcinoma, with a focus on the identification of possible combinatorial partners. We found that breast cancer control by LTX-315 is accompanied by a reconfiguration of the immunological tumor microenvironment that supports the activation of anticancer immunity and can be boosted by radiation therapy. Mechanistically, depletion of natural killer (NK) cells compromised the capacity of LTX-315 to limit local and systemic disease progression in a mouse model of triple-negative breast cancer, and to extend the survival of mice bearing hormone-accelerated, carcinogen-driven endogenous mammary carcinomas. Altogether, our data suggest that LTX-315 controls breast cancer progression by engaging NK cell-dependent immunity.

publication date

  • August 10, 2021

Research

keywords

  • Oligopeptides
  • Triple Negative Breast Neoplasms

Identity

PubMed Central ID

  • PMC8366543

Scopus Document Identifier

  • 85112254103

Digital Object Identifier (DOI)

  • 10.1038/s41577-019-0165-0

PubMed ID

  • 34408925

Additional Document Info

volume

  • 10

issue

  • 1