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Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

  • Sang-Hyun Kim (Department of Pharmaceutics, College of Pharmacy, Chungbuk National University) ;
  • Ha-Eun Park (Department of Pharmaceutics, College of Pharmacy, Chungbuk National University) ;
  • Seong-Un Jeong (Department of Pharmaceutics, College of Pharmacy, Chungbuk National University) ;
  • Jun-Hyeok Moon (Department of Pharmaceutics, College of Pharmacy, Chungbuk National University) ;
  • Young-Ran Lee (Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology) ;
  • Jeong-Ki Kim (Department of Pharmacy, Korea University College of Pharmacy) ;
  • Hyunseok Kong (Department of Animal Biotechnology and Resource, Sahmyook University) ;
  • Chan-Su Park (Department of Pathology, The Johns Hopkins University School of Medicine) ;
  • Chong-Kil Lee (Department of Pharmaceutics, College of Pharmacy, Chungbuk National University)
  • Received : 2021.11.17
  • Accepted : 2021.12.15
  • Published : 2021.12.31
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Abstract

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2Kb complex-specific CD8+ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8+ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2020R1A2C1009484, MRC-2017R1A5A2015541).

References

  1. Durgeau A, Virk Y, Corgnac S, Mami-Chouaib F. Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. Front Immunol 2018;9:14.
  2. Malonis RJ, Lai JR, Vergnolle O. Peptide-based vaccines: current progress and future challenges. Chem Rev 2020;120:3210-3229.
  3. Wagner S, Mullins CS, Linnebacher M. Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens. World J Gastroenterol 2018;24:5418-5432.
  4. Tanna JG, Ulrey R, Williams KM, Hanley PJ. Critical testing and parameters for consideration when manufacturing and evaluating tumor-associated antigen-specific T cells. Cytotherapy 2019;21:278-288.
  5. Schietinger A, Philip M, Schreiber H. Specificity in cancer immunotherapy. Semin Immunol 2008;20:276-285.
  6. Minati R, Perreault C, Thibault P. A roadmap toward the definition of actionable tumor-specific antigens. Front Immunol 2020;11:583287.
  7. Olsen LR, Campos B, Barnkob MS, Winther O, Brusic V, Andersen MH. Bioinformatics for cancer immunotherapy target discovery. Cancer Immunol Immunother 2014;63:1235-1249.
  8. Pallerla S, Abdul AU, Comeau J, Jois S. Cancer vaccines, treatment of the future: With emphasis on her2-positive breast cancer. Int J Mol Sci 2021;22:22.
  9. Cho HI, Barrios K, Lee YR, Linowski AK, Celis E. BiVax: a peptide/poly-IC subunit vaccine that mimics an acute infection elicits vast and effective anti-tumor CD8 T-cell responses. Cancer Immunol Immunother 2013;62:787-799.
  10. Barrios K, Celis E. TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers. Cancer Immunol Immunother 2012;61:1307-1317.
  11. Kumai T, Kobayashi H, Harabuchi Y, Celis E. Peptide vaccines in cancer-old concept revisited. Curr Opin Immunol 2017;45:1-7.
  12. Kumai T, Fan A, Harabuchi Y, Celis E. Cancer immunotherapy: moving forward with peptide T cell vaccines. Curr Opin Immunol 2017;47:57-63.
  13. Ahonen CL, Doxsee CL, McGurran SM, Riter TR, Wade WF, Barth RJ, Vasilakos JP, Noelle RJ, Kedl RM. Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med 2004;199:775-784.
  14. He X, Abrams SI, Lovell JF. Peptide delivery systems for cancer vaccines. Adv Ther 2018;1:1800060.
  15. Khong H, Overwijk WW. Adjuvants for peptide-based cancer vaccines. J Immunother Cancer 2016;4:56.
  16. Xia F, Qian CR, Xun Z, Hamon Y, Sartre AM, Formisano A, Mailfert S, Phelipot MC, Billaudeau C, Jaeger S, et al. TCR and CD28 concomitant stimulation elicits a distinctive calcium response in naive T cells. Front Immunol 2018;9:2864.
  17. Davis SJ, Ikemizu S, Evans EJ, Fugger L, Bakker TR, van der Merwe PA. The nature of molecular recognition by T cells. Nat Immunol 2003;4:217-224.
  18. Raskov H, Orhan A, Christensen JP, Gogenur I. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy. Br J Cancer 2021;124:359-367.
  19. Jeong S, Park SH. Co-stimulatory receptors in cancers and their implications for cancer immunotherapy. Immune Netw 2020;20:e3.
  20. Im SJ, Ha SJ. Re-defining T-cell exhaustion: subset, function, and regulation. Immune Netw 2020;20:e2.
  21. Jung HH, Kim SH, Moon JH, Jeong SU, Jang S, Park CS, Lee CK. Polymeric nanoparticles containing both antigen and vitamin D3 induce antigen-specific immune suppression. Immune Netw 2019;19:e19.
  22. Lee YH, Lee YR, Kim KH, Im SA, Song S, Lee MK, Kim Y, Hong JT, Kim K, Lee CK. Baccatin III, a synthetic precursor of taxol, enhances MHC-restricted antigen presentation in dendritic cells. Int Immunopharmacol 2011;11:985-991.
  23. Oyewumi MO, Kumar A, Cui Z. Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines 2010;9:1095-1107.
  24. Sadat SM, Jahan ST, Haddadi A. Effects of size and surface charge of polymeric nanoparticles on in vitro and in vivo applications. J Biomater Nanobiotechnol 2016;7:91-108.
  25. Lou D, Ji L, Fan L, Ji Y, Gu N, Zhang Y. Antibody-oriented strategy and mechanism for the preparation of fluorescent nanoprobes for fast and sensitive immunodetection. Langmuir 2019;35:4860-4867.
  26. Slingluff CL Jr. The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer J 2011;17:343-350.
  27. Dellacherie MO, Li AW, Lu BY, Mooney DJ. Covalent conjugation of peptide antigen to mesoporous silica rods to enhance cellular responses. Bioconjug Chem 2018;29:733-741.
  28. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm 2005;298:315-322.
  29. Kurts C, Robinson BW, Knolle PA. Cross-priming in health and disease. Nat Rev Immunol 2010;10:403-414.
  30. Chen L, Fabian KL, Taylor JL, Storkus WJ. Therapeutic use of dendritic cells to promote the extranodal priming of anti-tumor immunity. Front Immunol 2013;4:388.
  31. Schiavoni G, Mattei F, Gabriele L. Type I interferons as stimulators of DC-mediated cross-priming: impact on anti-tumor response. Front Immunol 2013;4:483.
  32. Rundqvist H, Velica P, Barbieri L, Gameiro PA, Bargiela D, Gojkovic M, Mijwel S, Reitzner SM, Wulliman D, Ahlstedt E, et al. Cytotoxic T-cells mediate exercise-induced reductions in tumor growth. eLife 2020;9:9.
  33. Gong Y, Suzuki T, Kozono H, Kubo M, Nakano N. Tumor-infiltrating CD62L+PD-1-CD8 T cells retain proliferative potential via Bcl6 expression and replenish effector T cells within the tumor. PLoS One 2020;15:e0237646.
  34. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 1994;264:961-965.
  35. Arina A, Tirapu I, Alfaro C, Rodriguez-Calvillo M, Mazzolini G, Inoges S, Lopez A, Feijoo E, Bendandi M, Melero I. Clinical implications of antigen transfer mechanisms from malignant to dendritic cells. exploiting cross-priming. Exp Hematol 2002;30:1355-1364.
  36. Wang Q, Wang J, Lu Q, Detamore MS, Berkland C. Injectable PLGA based colloidal gels for zero-order dexamethasone release in cranial defects. Biomaterials 2010;31:4980-4986.
  37. Hamdy S, Haddadi A, Hung RW, Lavasanifar A. Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations. Adv Drug Deliv Rev 2011;63:943-955.
  38. Keegan ME, Royce SM, Fahmy T, Saltzman WM. In vitro evaluation of biodegradable microspheres with surface-bound ligands. J Control Release 2006;110:574-580.
  39. Cao J, Choi JS, Oshi MA, Lee J, Hasan N, Kim J, Yoo JW. Development of PLGA micro- and nanorods with high capacity of surface ligand conjugation for enhanced targeted delivery. Asian J Pharm Sci 2019;14:86-94.