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Cell surface-tethered IL-12 repolarizes the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy. | LitMetric

AI Article Synopsis

  • Immune-activating cytokines like interleukin-12 (IL-12) have potential in cancer treatment but can cause high systemic toxicities.
  • Researchers developed a method to attach IL-12 directly to tumor-specific T cells, improving their effectiveness without the side effects of using IL-12 systemically.
  • This new approach not only enhances T cell activity at the tumor site but also reprograms the tumor's immune environment to support anti-cancer responses.

Article Abstract

Immune-activating cytokines such as interleukin-12 (IL-12) hold strong potential for cancer immunotherapy but have been limited by high systemic toxicities. We describe here an approach to safely harness cytokine biology for adoptive cell therapy through uniform and dose-controlled tethering onto the surface of the adoptively transferred cells. Tumor-specific T cells tethered with IL-12 showed superior antitumor efficacy across multiple cell therapy models compared to conventional systemic IL-12 coadministration. Mechanistically, the IL-12-tethered T cells supported a strong safety profile by driving interferon-γ production and adoptively transferred T cell activity preferentially in the tumor. Immune profiling revealed that the tethered IL-12 reshaped the suppressive tumor immune microenvironment, including triggering a pronounced repolarization of monocytic myeloid-derived suppressor cells into activated, inflammatory effector cells that further supported antitumor activity. This tethering approach thus holds strong promise for harnessing and directing potent immunomodulatory cytokines for cell therapies while limiting systemic toxicities.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045725PMC
http://dx.doi.org/10.1126/sciadv.abi8075DOI Listing

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