Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) elicits a strong and durable therapeutic response, but its application is limited by disparate responses and its associated immune-related adverse events (irAEs). Previously, in a murine model of lymph node (LN) metastasis, we showed that intranodal administration of chemotherapeutic agents using a lymphatic drug delivery system (LDDS) elicits stronger therapeutic responses in comparison to systemic drug delivery approaches, while minimizing systemic toxicity, due to its improved pharmacokinetic profile at the intended site. Importantly, the LN is a reservoir of immunotherapeutic targets. We therefore hypothesized that metastatic LN-targeted ICB can amplify anti-tumor response and uncouple it from ICB-induced irAEs.

Methods

To test

SUBMITTER: Mishra R 

PROVIDER: S-EPMC10233978 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature