Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression

Johann, K.; Bohn, T.; Shahneh, F.; Luther, N.; Birke , A.; Jaurich, H.; ... ; Becker, C. (2021)

Article / Letter to editor

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.

• All authors: Johann, K.; Bohn, T.; Shahneh, F.; Luther, N.; Birke , A.; Jaurich, H.; Helm, M.; Klein, M.; Raker, V.K.; Bopp, T.; Barz, M.; Becker, C.
• Date: 2021-11-13
• Journal: Nature Communications
• Volume: 12
• Issue: 1
• DOI: doi:10.1038/s41467-021-26269-w