Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma.

ABSTRACT: The use of specific anti-tumor antibodies has transformed the solid cancer therapeutics landscape with the relative successes of therapies such as anti-HER2 in breast cancer, and anti-EGFR in HNSCC and colorectal cancer. However, these therapies result in toxicity and the emergence of resistant tumors. Here, we showed that removing immune suppression and enhancing stimulatory signals increased the anti-tumor activity of unmodified TA99 antibodies (anti-TYRP1) with a significant reduction of growth of solid tumors and lung metastases in mouse models of melanoma. Immune checkpoint blockade enhanced the efficacy of TA99, which was associated with greater CD8⁺/Foxp3⁺, NK1.1⁺ and dendritic cell infiltrates, suggestive of an increased anti-tumor innate and adapti

SUBMITTER: Perez-Lorenzo R 

PROVIDER: S-EPMC7825641 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature