Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Giorgio Frega; Qi Wu; Julie Le Naour; Erika Vacchelli; Lorenzo Galluzzi; Guido Kroemer; Oliver Kepp

doi:10.1080/2162402X.2020.1796002

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Oncoimmunology. 2020 Jul 21;9(1):1796002. doi: 10.1080/2162402X.2020.1796002.

Authors

Giorgio Frega^{1

2

3}, Qi Wu^{1

2}, Julie Le Naour^{1

2}, Erika Vacchelli^{1

2}, Lorenzo Galluzzi^{4

5

6

7

8}, Guido Kroemer^{1

2

9

10

11}, Oliver Kepp^{1

2}

Affiliations

¹ Equipe labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Paris, France.
² Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.
³ Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
⁴ Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
⁵ Sandra and Edward Meyer Cancer Center, New York, NY, USA.
⁶ Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
⁷ Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
⁸ Université de Paris, Paris, France.
⁹ Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
¹⁰ Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
¹¹ Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents.

Keywords: CGAS; Cancer immunotherapy; danger signaling; immune checkpoint blockers; immunogenic cell death; type I interferon.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Adjuvants, Immunologic / pharmacology
Antineoplastic Agents* / pharmacology
Imiquimod
Toll-Like Receptor 7*
Toll-Like Receptor 8
United States

Substances

Adjuvants, Immunologic
Antineoplastic Agents
Toll-Like Receptor 7
Toll-Like Receptor 8
Imiquimod