Therapeutic Melanoma Inhibition by Local Micelle-mediated Cyclic Nucleotide Repression

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Oct 14

PMID 34645812

Citations 9

Authors

Kerstin Johann

Toszka Bohn

Fatemeh Shahneh

Natascha Luther

Alexander Birke

Henriette Jaurich

Mark Helm

Matthias Klein

Verena K Raker

Tobias Bopp

Matthias Barz

Christian Becker

Affiliations

Soon will be listed here.

Abstract

The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape.

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