Effects of Arylsulfatase B and Pembrolizumab in Combination on Progression of Metastatic Melanoma in the B16F10 Syngeneic Mouse Model

ABSTRACT In this report, experiments assessed how Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) treatment might interact with Pembrolizumab and improve therapeutic responses in melanoma. ARSB acts to remove 4-sulfate groups from chondroitin 4-sulfate (C4S; chondroitin sulfate A; CSA). ARSB is required for the degradation of C4S, identified as an oncofetal, tumor-agnostic antigen. Previous reports showed that in syngeneic B16F10 mouse melanomas, ARSB inhibited progression of subcutaneous and metastatic pulmonary melanomas and improved survival by direct effects on melanoma cells. ARSB enhanced apoptosis, which was mediated by increased expression of Constitutive Photomorphogenic (COP)1, an E3 ubiquitin ligase. Combined treatment by recombinant human ARSB, directed at melanoma cells, and Pembrolizumab, directed at infiltrating cytotoxic lymphocytes, can lead to increased apoptosis by different mechanisms, to declines in metalloproteinases and invasiveness, and to altered expression of cytokines. The apparent synergism between effects of ARSB and Pembrolizumab may further inhibit the progression of melanoma and improve treatment outcomes.