From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

Author:

Synoradzki Kamil J.1ORCID,Paduszyńska Natalia23,Solnik Malgorzata23ORCID,Toro Mario Damiano45ORCID,Bilmin Krzysztof6,Bylina Elżbieta37,Rutkowski Piotr3ORCID,Yousef Yacoub A.8ORCID,Bucolo Claudio9ORCID,Zweifel Sandrine Anne1011ORCID,Reibaldi Michele12ORCID,Fiedorowicz Michal13ORCID,Czarnecka Anna M.314ORCID

Affiliation:

1. Environmental Laboratory of Pharmacological and Toxicological Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland

2. Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland

3. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 5 Roentgen Str., 02-781 Warsaw, Poland

4. Chair and Department of General and Pediatric Ophthalmology, Medical University of Lublin, 1 Chmielna Str., 20-079 Lublin, Poland

5. Eye Clinic, Public Health Department, Federico II University, Via Pansini 5, 80131 Naples, Italy

6. Research and Development Centre Novasome Sp. z o.o., 51-423 Wrocław, Poland

7. Department of Clinical Trials, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland

8. Department of Surgery (Ophthalmology), King Hussein Cancer Centre, Amman 11941, Jordan

9. Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy

10. Department of Ophthalmology, University Hospital Zurich, 8091 Zurich, Switzerland

11. Faculty of Human Medicine, University of Zurich, 8032 Zurich, Switzerland

12. Department of Surgical Sciences, Eye Clinic Section, Citta della Salute e della Scienza, Turin University, 10122 Turin, Italy

13. Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland

14. Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland

Abstract

Molecular biology studies of uveal melanoma have resulted in the development of novel immunotherapy approaches including tebentafusp—a T cell–redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined immunotherapy is being developed as well as immunotherapy with bifunctional checkpoint inhibitory T cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination with IKKb-matured dendritic cells, or autologous dendritic cells loaded with autologous tumor RNA. Another potential approach to treat UM could be based on T cell receptor engineering rather than antibody modification. Immune-mobilizing monoclonal T cell receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, are promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis and therapy with the same molecule bring hope to this research.

Funder

University of Naples Federico II

Publisher

MDPI AG

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