Tumour-derived Extracellular Vesicle Based Vaccines for Melanoma Treatment

Overview

Journal Drug Deliv Transl Res

Publisher Springer

Specialty Pharmacology

Date 2023 Apr 6

PMID 37022605

Authors

Lorena Gonzalez-Melero

Rosa Maria Hernandez

Edorta Santos-Vizcaino

Manoli Igartua

Affiliations

Soon will be listed here.

Abstract

The interest of extracellular vesicles (EVs) in cancer immunotherapy is increasing every day. EVs are lipid bilayer vesicles released by most cells, which contain the molecular signature of their parent cell. Melanoma-derived EVs present antigens specific to this aggressive type of cancer, but they also exert immunomodulatory and pro-metastatic activity. Until now, most reviews focus on the immunoevasive characteristics of tumour-derived EVs, but do not help to overcome the issues related to them. In this review, we describe isolation methods of EVs from melanoma patients and most interesting markers to oversee their effect if they are used as antigen carriers. We also discuss the methods developed so far to overcome the lack of immunogenicity of melanoma-derived EVs, which includes EV modification or adjuvant co-administration. In summary, we conclude that EVs can be an interesting antigen source for immunotherapy development once EV obtaining is optimised and the understanding of the mechanisms behind their multiple effects is further understood.

Citing Articles

Grapefruit-Derived Vesicles Loaded with Recombinant HSP70 Activate Antitumor Immunity in Colon Cancer In Vitro and In Vivo.

Garaeva L, Komarova E, Emelianova S, Putevich E, Konevega A, Margulis B Biomedicines. 2025; 12(12.

PMID: 39767665 PMC: 11674020. DOI: 10.3390/biomedicines12122759.

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery.

Al-Jipouri A, Eritja A, Bozic M Int J Mol Sci. 2024; 25(1).

PMID: 38203656 PMC: 10779093. DOI: 10.3390/ijms25010485.

Tumor-associated macrophages as a potential therapeutic target in thyroid cancers.

Zhu L, Li X, Gangadaran P, Jing X, Ahn B Cancer Immunol Immunother. 2023; 72(12):3895-3917.

PMID: 37796300 PMC: 10992981. DOI: 10.1007/s00262-023-03549-6.

Human Papillomavirus-Associated Tumor Extracellular Vesicles in HPV Tumor Microenvironments.

Gameiro S, Flondra K J Clin Med. 2023; 12(17).

PMID: 37685735 PMC: 10488665. DOI: 10.3390/jcm12175668.

References

Wang M, Altinoglu S, Takeda Y, Xu Q . Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery. PLoS One. 2015; 10(11):e0141860. PMC: 4631329. DOI: 10.1371/journal.pone.0141860. View

Crescitelli R, Lasser C, Jang S, Cvjetkovic A, Malmhall C, Karimi N . Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation. J Extracell Vesicles. 2020; 9(1):1722433. PMC: 7034452. DOI: 10.1080/20013078.2020.1722433. View

Zhou L, Yang K, Wickett R, Zhang Y . Dermal fibroblasts induce cell cycle arrest and block epithelial-mesenchymal transition to inhibit the early stage melanoma development. Cancer Med. 2016; 5(7):1566-79. PMC: 4944884. DOI: 10.1002/cam4.707. View

Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N . Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Front Immunol. 2017; 8:403. PMC: 5380675. DOI: 10.3389/fimmu.2017.00403. View

Bonnefoy N, Bastid J, Alberici G, Bensussan A, Eliaou J . CD39: A complementary target to immune checkpoints to counteract tumor-mediated immunosuppression. Oncoimmunology. 2015; 4(5):e1003015. PMC: 4485743. DOI: 10.1080/2162402X.2014.1003015. View

Kim W, Choi D, Park J, Song H, Seo H, Lee D . Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine. Vaccines (Basel). 2020; 8(4). PMC: 7712075. DOI: 10.3390/vaccines8040699. View

Boussadia Z, Lamberti J, Mattei F, Pizzi E, Puglisi R, Zanetti C . Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J Exp Clin Cancer Res. 2018; 37(1):245. PMC: 6173926. DOI: 10.1186/s13046-018-0915-z. View

Lazar I, Clement E, Ducoux-Petit M, Denat L, Soldan V, Dauvillier S . Proteome characterization of melanoma exosomes reveals a specific signature for metastatic cell lines. Pigment Cell Melanoma Res. 2015; 28(4):464-75. DOI: 10.1111/pcmr.12380. View

Meldolesi J . Exosomes and Ectosomes in Intercellular Communication. Curr Biol. 2018; 28(8):R435-R444. DOI: 10.1016/j.cub.2018.01.059. View

10.

Crescitelli R, Lasser C, Lotvall J . Isolation and characterization of extracellular vesicle subpopulations from tissues. Nat Protoc. 2021; 16(3):1548-1580. DOI: 10.1038/s41596-020-00466-1. View

11.

Leiter U, Keim U, Garbe C . Epidemiology of Skin Cancer: Update 2019. Adv Exp Med Biol. 2020; 1268:123-139. DOI: 10.1007/978-3-030-46227-7_6. View

12.

Andre F, Schartz N, Movassagh M, Flament C, Pautier P, Morice P . Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002; 360(9329):295-305. DOI: 10.1016/S0140-6736(02)09552-1. View

13.

Morishita M, Takahashi Y, Matsumoto A, Nishikawa M, Takakura Y . Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. Biomaterials. 2016; 111:55-65. DOI: 10.1016/j.biomaterials.2016.09.031. View

14.

Yamauchi T, Moroishi T . The Yin and Yang of tumour-derived extracellular vesicles in tumour immunity. J Biochem. 2020; 169(2):155-161. DOI: 10.1093/jb/mvaa132. View

15.

Li X, Liu Y, Yang L, Jiang Y, Qian Q . TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4 T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells. Transl Oncol. 2022; 18:101334. PMC: 8808081. DOI: 10.1016/j.tranon.2021.101334. View

16.

Ferrari de Andrade L, Tay R, Pan D, Luoma A, Ito Y, Badrinath S . Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science. 2018; 359(6383):1537-1542. PMC: 6626532. DOI: 10.1126/science.aao0505. View

17.

Price M, Colvin Wanshura L, Yang J, Carlson J, Xiang B, Li G . CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma. Pigment Cell Melanoma Res. 2011; 24(6):1148-57. PMC: 3426219. DOI: 10.1111/j.1755-148X.2011.00929.x. View

18.

Kappelmann M, Kuphal S, Meister G, Vardimon L, Bosserhoff A . MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene. 2012; 32(24):2984-91. DOI: 10.1038/onc.2012.307. View

19.

Campos-Silva C, Kramer M, Vales-Gomez M . NKG2D-ligands: Putting everything under the same umbrella can be misleading. HLA. 2018; 91(6):489-500. DOI: 10.1111/tan.13246. View

20.

Vergani E, Daveri E, Vallacchi V, Bergamaschi L, Lalli L, Castelli C . Extracellular vesicles in anti-tumor immunity. Semin Cancer Biol. 2021; 86(Pt 1):64-79. DOI: 10.1016/j.semcancer.2021.09.004. View