Tofacitinib enhances delivery of antibody-based therapeutics to tumor cells through modulation of inflammatory cells.

ABSTRACT: The routes by which antibody-based therapeutics reach malignant cells are poorly defined. Tofacitinib, an FDA-approved JAK inhibitor, reduced tumor-associated inflammatory cells and allowed increased delivery of antibody-based agents to malignant cells. Alone, tofacitinib exhibited no antitumor activity, but combinations with immunotoxins or an antibody-drug conjugate resulted in increased antitumor responses. Quantification using flow cytometry revealed that antibody-based agents accumulated in malignant cells at higher percentages following tofacitinib treatment. Profiling of tofacitinib-treated tumor-bearing mice indicated that cytokine transcripts and various proteins involved in chemotaxis were reduced compared with vehicle-treated mice. Histological analysis revealed significant chan

SUBMITTER: Simon N 

PROVIDER: S-EPMC6483512 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature