Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy.

ABSTRACT: Systemic administration of immune checkpoint blockade (ICB) monoclonal antibodies (mAbs) can unleash antitumor functions of T cells but is associated with variable response rates and off-target toxicities. We hypothesized that antitumor efficacy of ICB is limited by the minimal accumulation of mAb within tissues where antitumor immunity is elicited and regulated, which include the tumor microenvironment (TME) and secondary lymphoid tissues. In contrast to systemic administration, intratumoral and intradermal routes of administration resulted in higher mAb accumulation within both the TME and its draining lymph nodes (LNs) or LNs alone, respectively. The use of either locoregional administration route resulted in pronounced T cell responses from the ICB therapy, which developed in the secon

SUBMITTER: Francis DM 

PROVIDER: S-EPMC8377700 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature