Reviews in Clinical Medicine

Reviews in Clinical Medicine

Strategies and Challenges for Developing Effective Neoantigen-Based Dendritic Cell Vaccines for Cancer Immunotherapy: A Literature Review

Document Type : Review

Authors
Seyed Mohammad Javadzadeh 1
Mehdi Barati 2
Amirali Ghahremani 3
Hasan Namdar Ahmadabad 2
1 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia
2 Vector-borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
3 Department of Internal Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
10.22038/rcm.2025.86466.1530
Abstract
Dendritic cells (DCs) are pivotal in the field of cancer immunotherapy due to their unique ability to initiate and modulate robust immune responses. Therefore, they represent a promising strategy for cancer vaccine development. Nonetheless, the efficacy of DC vaccines is hampered by the immunosuppressive microenvironment that is frequently present in tumors, which poses significant challenges to their effectiveness. Recent research has focused on two primary approaches to enhance DC vaccine outcomes. The first strategy involves the synergistic use of DC vaccines along with immune checkpoint inhibitors, traditional chemotherapy, or monospecific/bispecific antibodies to bolster immune activation. The second strategy emphasizes the identification and selection of tumor antigens that are not only specific and immunogenic but also manifest safety and stability characteristics. Among these, personalized neoantigens, specific antigens that arise from the tumor microenvironment, have garnered particular attention in clinical trials and have emerged as ideal candidates for DC vaccine targeting. This literature review comprehensively discusses these challenges and strategically explores the pathways to develop effective and safe neoantigen-based DC vaccines for cancer immunotherapy.
Keywords
Cancer immunotherapy
Dendritic cell vaccine
Neoantigen vaccine
Personalized neoantigens
  1. Tan S, Li D, Zhu X. Cancer immunotherapy: Pros, cons and beyond. Biomedicine & Pharmacotherapy. 2020;124:109821.
  2. Booth S. Pros and Cons of Immunotherapy United States WebMed; 2023 [updated March 12, 2023. Available from: https://www.webmd.com/cancer/immunotherapy-risks-benefits.
  3. Esfahani K, Roudaia L, Buhlaiga N, Del Rincon S, Papneja N, Miller W. A review of cancer immunotherapy: from the past, to the present, to the future. Current Oncology. 2020;27(s2):87-97.
  4. Barati M, Mirzavi F, Nikpoor AR, Sankian M, Namdar Ahmadabad H, Soleimani A, et al. Enhanced antitumor immune response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes. Cancer gene therapy. 2022;29(6):814-24.
  5. Hayes C. Cellular immunotherapies for cancer. Irish Journal of Medical Science (1971-). 2021;190:41-57.
  6. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nature Reviews Immunology. 2015;15(8):486-99.
  7. Bai R, Lv Z, Xu D, Cui J. Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors. Biomarker research. 2020;8:1-17.
  8. Queirolo P, Boutros A, Tanda E, Spagnolo F, Quaglino P, editors. Immune-checkpoint inhibitors for the treatment of metastatic melanoma: a model of cancer immunotherapy. Seminars in cancer biology; 2019: Elsevier.
  9. Tang S, Qin C, Hu H, Liu T, He Y, Guo H, et al. Immune checkpoint inhibitors in non-small cell lung cancer: progress, challenges, and prospects. Cells. 2022;11(3):320.
  10. Marei HE, Hasan A, Pozzoli G, Cenciarelli C. Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired. Cancer Cell International. 2023;23(1):64.
  11. Yu J, Sun H, Cao W, Song Y, Jiang Z. Research progress on dendritic cell vaccines in cancer immunotherapy. Experimental Hematology & Oncology. 2022;11(1):1-22.
  12. Stevens D, Ingels J, Van Lint S, Vandekerckhove B, Vermaelen K. Dendritic cell-based immunotherapy in lung cancer. Frontiers in immunology. 2021;11:620374.
  13. Matsuo K, Yoshie O, Kitahata K, Kamei M, Hara Y, Nakayama T. Recent progress in dendritic cell-based cancer immunotherapy. Cancers. 2021;13(10):2495.
  14. Fritah HG, Rovelli R, Chiang CL-L, Kandalaft LE. The current clinical landscape of personalized cancer vaccines. Cancer Treatment Reviews. 2022:102383.
  15. Shemesh CS, Hsu JC, Hosseini I, Shen B-Q, Rotte A, Twomey P, et al. Personalized cancer vaccines: clinical landscape, challenges, and opportunities. Molecular Therapy. 2021;29(2):555-70.
  16. Ahmadabad HN, Hassan ZM, Safari E, Bozorgmehr M, Ghazanfari T, Moazzeni SM. Evaluation of the immunomodulatory effect of the 14 kDa protein isolated from aged garlic extract on dendritic cells. Cellular immunology. 2011;269(2):90-5.
  17. Mroz EA, Rocco JW. The challenges of tumor genetic diversity. Cancer. 2017;123(6):917-27.
  18. Pearlman AH, Hwang MS, Konig MF, Hsiue EH-C, Douglass J, DiNapoli SR, et al. Targeting public neoantigens for cancer immunotherapy. Nature cancer. 2021;2(5):487-97.
  19. Hannani D, Leplus E, Laulagnier K, Chaperot L, Plumas J. Leveraging a powerful allogeneic dendritic cell line towards neoantigen-based cancer vaccines. Genes & Cancer. 2023;14:3.
  20. Peng M, Mo Y, Wang Y, Wu P, Zhang Y, Xiong F, et al. Neoantigen vaccine: an emerging tumor immunotherapy. Molecular cancer. 2019;18(1):1-14.
  21. Andersen MH, editor Tumor microenvironment antigens. Seminars in Immunopathology; 2023: Springer.
  22. Li L, Goedegebuure SP, Gillanders W. Cancer vaccines: shared tumor antigens return to the spotlight. Signal transduction and targeted therapy. 2020;5(1):251.
  23. Feola S, Chiaro J, Martins B, Cerullo V. Uncovering the tumor antigen landscape: what to know about the discovery process. Cancers. 2020;12(6):1660.
  24. Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. npj Vaccines. 2019;4(1):7.
  25. Fu C, Zhao H, Wang Y, Cai H, Xiao Y, Zeng Y, et al. Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen. Hla. 2016;88(6):275-86.
  26. Ilyas S, Yang JC. Landscape of tumor antigens in T cell immunotherapy. The Journal of Immunology. 2015;195(11):5117-22.
  27. Nurieva R, Divenko M, Kim S. Cancer immunology and the evolution of immunotherapy. Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy: A Handbook for Diagnosis and Management. 2021:3-29.
  28. Yan T, Zhu L, Chen J. Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment. Experimental Hematology & Oncology. 2023;12(1):14.
  29. Zhu G, Zhang Q, Zhang J, Liu F. Targeting tumor-associated antigen: a promising CAR-T therapeutic strategy for glioblastoma treatment. Frontiers in Pharmacology. 2021;12:661606.
  30. Desrichard A, Snyder A, Chan TA. Cancer Neoantigens and Applications for ImmunotherapyNeoantigens and Immunotherapy. Clinical Cancer Research. 2016;22(4):807-12.
  31. Pan R-Y, Chung W-H, Chu M-T, Chen S-J, Chen H-C, Zheng L, et al. Recent development and clinical application of cancer vaccine: targeting neoantigens. Journal of immunology research. 2018;2018.
  32. Lang F, Schrörs B, Löwer M, Türeci Ö, Sahin U. Identification of neoantigens for individualised cancer immunotherapy. Nat Rev Drug Discov. 2022;21(4):261-82.
  33. Yu G, Pang Y, Merchant M, Kesserwan C, Gangalapudi V, Abdelmaksoud A, et al. Tumor mutation burden, expressed neoantigens and the immune microenvironment in diffuse gliomas. Cancers. 2021;13(23):6092.
  34. Xie N, Shen G, Gao W, Huang Z, Huang C, Fu L. Neoantigens: promising targets for cancer therapy. Signal Transduction and Targeted Therapy. 2023;8(1):9.
  35. Tang L, Zhang R, Zhang X, Yang L. Personalized neoantigen-pulsed DC vaccines: advances in clinical applications. Frontiers in Oncology. 2021;11:701777.
  36. Reynolds CR, Tran S, Jain M, Narendran A. Neoantigen cancer vaccines: generation, optimization, and therapeutic targeting strategies. Vaccines. 2022;10(2):196.
  37. Eshkiki ZS, Agah S, Tabaeian SP, Sedaghat M, Dana F, Talebi A, et al. Neoantigens and their clinical applications in human gastrointestinal cancers. World Journal of Surgical Oncology. 2022;20(1):1-15.
  38. Peng S, Zaretsky JM, Ng AH, Chour W, Bethune MT, Choi J, et al. Sensitive detection and analysis of neoantigen-specific T cell populations from tumors and blood. Cell reports. 2019;28(10):2728-38. e7.
  39. Kast F, Klein C, Umaña P, Gros A, Gasser S. Advances in identification and selection of personalized neoantigen/T-cell pairs for autologous adoptive T cell therapies. OncoImmunology. 2021;10(1):1869389.
  40. Liao J-Y, Zhang S. Safety and efficacy of personalized cancer vaccines in combination with immune checkpoint inhibitors in cancer treatment. Frontiers in Oncology. 2021;11:663264.
  41. Ali M, Foldvari Z, Giannakopoulou E, Böschen M-L, Strønen E, Yang W, et al. Induction of neoantigen-reactive T cells from healthy donors. Nature protocols. 2019;14(6):1926-43.
  42. Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nature Reviews Clinical Oncology. 2021;18(4):215-29.
  43. Roerden M, Castro AB, Cui Y, Harake N, Kim B, Dye J, et al. Neoantigen architectures define immunogenicity and drive immune evasion of tumors with heterogenous neoantigen expression. Journal for ImmunoTherapy of Cancer. 2024;12(11):e010249.
  44. Katsikis PD, Ishii KJ, Schliehe C. Challenges in developing personalized neoantigen cancer vaccines. Nature Reviews Immunology. 2024;24(3):213-27.
  45. Chu Y, Liu Q, Wei J, Liu B. Personalized cancer neoantigen vaccines come of age. Theranostics. 2018;8(15):4238.
  46. Zhang Z, Lu M, Qin Y, Gao W, Tao L, Su W, et al. Neoantigen: A new breakthrough in tumor immunotherapy. Frontiers in Immunology. 2021;12:672356.
  47. Bullock T. Enhanced Melanoma Vaccine Against Neoantigens and Shared Antigens by CD40 Activation and TLR Agonists. University of Virginia Charlottesville United States; 2020.
  48. Ni Q, Zhang F, Liu Y, Wang Z, Yu G, Liang B, et al. A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer. Science advances. 2020;6(12):eaaw6071.
  49. Poorebrahim M, Mohammadkhani N, Mahmoudi R, Gholizadeh M, Fakhr E, Cid-Arregui A. Correction: TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential. Cancer Gene Therapy. 2021;28(6):738.
  50. Ding Z, Li Q, Zhang R, Xie L, Shu Y, Gao S, et al. Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer. Signal transduction and targeted therapy. 2021;6(1):26.
  51. Lhuillier C, Rudqvist N-P, Yamazaki T, Zhang T, Charpentier M, Galluzzi L, et al. Radiotherapy-exposed CD8+ and CD4+ neoantigens enhance tumor control. The Journal of clinical investigation. 2021;131(5).
  52. Leung CSK, Van den Eynde BJ. Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. Cancer Cell. 2022;40(9):903-5.
  53. Zhang X, Xu Z, Dai X, Zhang X, Wang X. Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer. Frontiers in Immunology. 2023;14:51.
  54. Ingels J, De Cock L, Stevens D, Mayer RL, Théry F, Sanchez GS, et al. Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum. Cell Reports Medicine. 2024;5(5).
  55. Cabeza-Cabrerizo M, Cardoso A, Minutti CM, Pereira da Costa M, Reis e Sousa C. Dendritic cells revisited. Annual review of immunology. 2021;39:131-66.
  56. Lellahi SM, Azeem W, Hua Y, Gabriel B, Rye KP, Reikvam H, et al. GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2. Frontiers in Immunology. 2022;13.
  57. Ahmadabad HN, Salehnia M, Saito S, Moazzeni SM. Decidual soluble factors, through modulation of dendritic cells functions, determine the immune response patterns at the feto-maternal interface. Journal of reproductive immunology. 2016;114:10-7.
  58. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nature Reviews Immunology. 2020;20(1):7-24.
  59. Patente TA, Pinho MP, Oliveira AA, Evangelista GC, Bergami-Santos PC, Barbuto JA. Human dendritic cells: their heterogeneity and clinical application potential in cancer immunotherapy. Frontiers in immunology. 2019;9:3176.
  60. Pourahmad R, Rezaei N. Role of Monocyte-Derived Dendritic Cells (MoDCs) in Tumor Immune Response. Handbook of Cancer and Immunology: Springer; 2023. p. 1-18.
  61. Rajak KK. Immunotherapy for cancer treatment. Understanding Cancer: Elsevier; 2022. p. 269-86.
  62. Filin IY, Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV. Recent advances in experimental dendritic cell vaccines for cancer. Frontiers in Oncology. 2021;11:730824.
  63. Ogasawara M, Miyashita M, Yamagishi Y, Ota S. Dendritic cell vaccination combined with a conventional chemotherapy for patients with relapsed or advanced pancreatic ductal adenocarcinoma: a single‐center phase I/II trial. Therapeutic Apheresis and Dialysis. 2021;25(4):415-24.
  64. van Willigen WW, Bloemendal M, Boers-Sonderen MJ, de Groot JWB, Koornstra RH, van der Veldt AA, et al. Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination. Oncoimmunology. 2020;9(1):1738814.
  65. Lim S, Park J-H, Chang H. Enhanced anti-tumor immunity of vaccine combined with anti-PD-1 antibody in a murine bladder cancer model. Investigative and Clinical Urology. 2023;64(1):74-81.
  66. Harari A, Graciotti M, Bassani-Sternberg M, Kandalaft LE. Antitumour dendritic cell vaccination in a priming and boosting approach. Nature Reviews Drug Discovery. 2020;19(9):635-52.
  67. Melero I, Gaudernack G, Gerritsen W, Huber C, Parmiani G, Scholl S, et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nature reviews Clinical oncology. 2014;11(9):509-24.
  68. Chiang CL-L, Coukos G, Kandalaft LE. Whole tumor antigen vaccines: where are we? Vaccines. 2015;3(2):344-72.
  69. Kamigaki T, Takimoto R, Okada S, Ibe H, Oguma E, Goto S. Personalized dendritic-cell-based vaccines targeting cancer neoantigens. Anticancer Research. 2024;44(9):3713-24.
  70. Li L, Goedegebuure S, Gillanders WE. Preclinical and clinical development of neoantigen vaccines. Annals of Oncology. 2017;28:xii11-xii7.
  71. Zhou X, Mo X, Qiu J, Zhao J, Wang S, Zhou C, et al. Chemotherapy combined with dendritic cell vaccine and cytokine-induced killer cells in the treatment of colorectal carcinoma: a meta-analysis. Cancer management and research. 2018;10:5363.
  72. Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell. 2020;183(2):347-62. e24.
  73. Kumari K, Singh A, Chaudhary A, Singh RK, Shanker A, Kumar V, et al. Neoantigen identification and dendritic cell-based vaccines for lung cancer immunotherapy. Vaccines. 2024;12(5):498.
  74. Verma C, Pawar VA, Srivastava S, Tyagi A, Kaushik G, Shukla SK, et al. Cancer vaccines in the immunotherapy era: promise and potential. Vaccines. 2023;11(12):1783.
  75. Zhang X, Xu Z, Dai X, Zhang X, Wang X. Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer. Frontiers in Immunology. 2023;14:1104860.
  76. Zhang R, Yuan F, Shu Y, Tian Y, Zhou B, Yi L, et al. Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models. Cancer Immunology, Immunotherapy. 2020;69:135-45.

 

 

Reviews in Clinical Medicine
Volume 12, Issue 2
Spring 2025
Pages 94-105