Neoantigen-specific MRNA/DC Vaccines for Effective Anticancer Immunotherapy

Overview

Journal Genes Immun

Date 2024 Nov 26

PMID 39592852

Authors

Wenli Zhang

Jiahao Guan

Wenwen Wang

Guo Chen

Li Fan

Zifan Lu

Affiliations

Soon will be listed here.

Abstract

The development of personalized anticancer vaccines based on neoantigens represents a new direction in cancer immunotherapy. The latest advancement in dendritic cell (DC) tumor vaccine construction involves loading DC with mRNA-encoding neoantigens, which allows for rapid production and is suitable for personalized preparation. Cell-penetrating peptides (CPPs) are emerging as biological delivery systems in which negatively charged nucleic acids can be wound onto the cationic CPP backbone to form nanoscale complexes. This preparation method facilitates standardization. If DC can express and present neoantigen mRNA at high levels, it holds promising application potential. In this study, we developed a neoantigen-mRNA/DC vaccine using candidate neoantigens from mouse colon cancer (MC38) and examined its immune and antitumor effects. The results demonstrated that neoantigen-mRNA/DC vaccines induced strong T cell immune responses and exhibited significant antitumor effects, effectively preventing tumor growth. Our study provides an experimental basis for further optimizing the preparation of DC vaccines and reducing their costs.

References

Lin M, Svensson-Arvelund J, Lubitz G, Marabelle A, Melero I, Brown B . Cancer vaccines: the next immunotherapy frontier. Nat Cancer. 2022; 3(8):911-926. DOI: 10.1038/s43018-022-00418-6. View

Wculek S, Cueto F, Mujal A, Melero I, Krummel M, Sancho D . Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2019; 20(1):7-24. DOI: 10.1038/s41577-019-0210-z. View

Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S . Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol. 2002; 20:621-67. DOI: 10.1146/annurev.immunol.20.100301.064828. View

Rowshanravan B, Halliday N, Sansom D . CTLA-4: a moving target in immunotherapy. Blood. 2017; 131(1):58-67. PMC: 6317697. DOI: 10.1182/blood-2017-06-741033. View

Chemnitz J, Parry R, Nichols K, June C, Riley J . SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004; 173(2):945-54. DOI: 10.4049/jimmunol.173.2.945. View

Flies D, Han X, Higuchi T, Zheng L, Sun J, Ye J . Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity. J Clin Invest. 2014; 124(5):1966-75. PMC: 4001557. DOI: 10.1172/JCI74589. View

Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H . Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012; 13(9):832-42. PMC: 3622453. DOI: 10.1038/ni.2376. View

Martinez-Usatorre A, Romero P . Generation of affinity ranged antigen-expressing tumor cell lines. Methods Enzymol. 2020; 632:503-519. DOI: 10.1016/bs.mie.2019.12.001. View

Finn O . Human Tumor Antigens Yesterday, Today, and Tomorrow. Cancer Immunol Res. 2017; 5(5):347-354. PMC: 5490447. DOI: 10.1158/2326-6066.CIR-17-0112. View

10.

Sahin U, Tureci O . Personalized vaccines for cancer immunotherapy. Science. 2018; 359(6382):1355-1360. DOI: 10.1126/science.aar7112. View

11.

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky J, Desrichard A . Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371(23):2189-2199. PMC: 4315319. DOI: 10.1056/NEJMoa1406498. View

12.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

13.

Balachandran V, Luksza M, Zhao J, Makarov V, Moral J, Remark R . Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017; 551(7681):512-516. PMC: 6145146. DOI: 10.1038/nature24462. View

14.

Heuts J, Varypataki E, van der Maaden K, Romeijn S, Drijfhout J, Terwisscha van Scheltinga A . Cationic Liposomes: A Flexible Vaccine Delivery System for Physicochemically Diverse Antigenic Peptides. Pharm Res. 2018; 35(11):207. PMC: 6156754. DOI: 10.1007/s11095-018-2490-6. View

15.

Sahin U, Derhovanessian E, Miller M, Kloke B, Simon P, Lower M . Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017; 547(7662):222-226. DOI: 10.1038/nature23003. View

16.

Maugeri M, Nawaz M, Papadimitriou A, Angerfors A, Camponeschi A, Na M . Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells. Nat Commun. 2019; 10(1):4333. PMC: 6760118. DOI: 10.1038/s41467-019-12275-6. View

17.

Akahoshi A, Matsuura E, Ozeki E, Matsui H, Watanabe K, Ohtsuki T . Enhanced cellular uptake of lactosomes using cell-penetrating peptides. Sci Technol Adv Mater. 2016; 17(1):245-252. PMC: 5101896. DOI: 10.1080/14686996.2016.1178056. View

18.

Van Asbeck A, Beyerle A, McNeill H, Bovee-Geurts P, Lindberg S, Verdurmen W . Molecular parameters of siRNA--cell penetrating peptide nanocomplexes for efficient cellular delivery. ACS Nano. 2013; 7(5):3797-807. DOI: 10.1021/nn305754c. View

19.

Deshayes S, Konate K, Rydstrom A, Crombez L, Godefroy C, Milhiet P . Self-assembling peptide-based nanoparticles for siRNA delivery in primary cell lines. Small. 2012; 8(14):2184-8. DOI: 10.1002/smll.201102413. View

20.

McCarthy H, McCaffrey J, McCrudden C, Zholobenko A, Ali A, McBride J . Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery. J Control Release. 2014; 189:141-9. DOI: 10.1016/j.jconrel.2014.06.048. View