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Anti-melanoma Effects of Resiquimod (RSQ) In Vitro and in Combination with Immune Checkpoint Blockade In Vivo

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  • Recent Advances in Drug Delivery
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Abstract

Melanoma is the deadliest form of skin cancer and surgery is currently the most effective treatment. However, there are situations where surgery fails or is not an option to treat melanoma patients. Immunotherapy such as immune checkpoint blockade (e.g., anti-PD-1) can be effective as an alternative treatment for melanoma patients; however, the percentage of melanoma patients that exhibit complete responses from anti-PD-1 monotherapy is low, and a hostile immunosuppressive tumor microenvironment may be at least partly responsible. Resiquimod (RSQ) is an imidazoquinolinamine derivative and TLR-7/8 agonist that could enhance the antitumor activity of immune checkpoint blockade when these agents are combined as a treatment for melanoma. Here, the effect of combining systemic anti-PD-1 and locally administered RSQ on the survival of melanoma-challenged mice was tested. Our results demonstrated that anti-PD-1 in combination with RSQ can significantly prolong the survival of melanoma-challenged mice, compared to untreated mice and mice treated with anti-PD-1 alone. In addition, the in vitro studies showed that RSQ can mediate a direct anti-proliferative effect on melanoma cells. In conclusion, the combination of RSQ and anti-PD-1 may be a promising treatment for melanoma patients, especially as both treatments have already been used independently to safely treat melanoma patients.

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Funding

A.K.S acknowledges support from the NIH (P30 CA086862) and the Lyle and Sharon Bighley Chair of Pharmaceutical Sciences. S.T acknowledges support from a Royal Thai Government Scholarship.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA

    Supreeda Tambunlertchai, Sean M. Geary, Youssef W. Naguib & Aliasger K. Salem

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  1. Supreeda Tambunlertchai
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  2. Sean M. Geary
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  3. Youssef W. Naguib
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  4. Aliasger K. Salem
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All authors contributed to the conception and design of the work as well as drafting, revising and final approval of the published manuscript.

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Correspondence to Sean M. Geary or Aliasger K. Salem.

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Tambunlertchai, S., Geary, S.M., Naguib, Y.W. et al. Anti-melanoma Effects of Resiquimod (RSQ) In Vitro and in Combination with Immune Checkpoint Blockade In Vivo. AAPS J 25, 57 (2023). https://doi.org/10.1208/s12248-023-00824-3

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