Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain.

ABSTRACT: CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8⁺ T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8⁺ T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy. Triple combination of ISF35, anti-PD-1, and anti-CTLA-4 results in complete eradication of injected and noninjected subcutaneous tumors, as well as melanoma tumors in the brain. Therapeutic efficacy is associated with incre

SUBMITTER: Singh M 

PROVIDER: S-EPMC5682289 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature