TGF-βRII/IL-15 immunotherapeutic complex targets exhausted CD8⁺ T-cell subsets in lymph nodes and tumors.

ABSTRACT:

Background

Stem-like progenitor exhausted CD8⁺ T cells (T_PEX), located within the tumor-draining lymph nodes (TDLNs), are responsible for maintaining tumor-specific responses in cancer. Although cytokines such as interleukin (IL)-15 are known to expand CD8⁺ T-cell subsets, transforming growth factor (TGF)-β in the TDLN is known to arrest the egress of these T_PEX to the tumor microenvironment. We hypothesized that combining IL-15 stimulatory and TGF-β blocking activity would boost antitumor responses mediated by T_PEX in the TDLN.

Methods

We developed a bifunctional TGF-βRII/IL-15 protein complex (HCW9218) and evaluated its antitumor activity in two murine models of melanoma and breast cancer. Peripheral blood, TDLN and tu

SUBMITTER: George VK 

PROVIDER: S-EPMC12719900 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature