Heat Shock Protein for Use in Cancer Vaccine Therapy: Immune Response and Immunotherapy

Trends in Immunotherapy

Review Article

Heat Shock Protein for Use in Cancer Vaccine Therapy: Immune Response and Immunotherapy

Downloads

https://doi.org/10.54963/ti.v9i4.1027
Lazokatkhon, D., Alhiti, H. A. R., Bakr, O. F., Shafiq, M. A., Al-Hilfi, T., & Karim, S. H. (2025). Heat Shock Protein for Use in Cancer Vaccine Therapy: Immune Response and Immunotherapy. Trends in Immunotherapy, 9(4), 130–145. https://doi.org/10.54963/ti.v9i4.1027
Volume 9 Issue 4 (December 2025): In Progress
Copyright (c) 2025 Dzhumaeva Lazokatkhon, Hazim Abdul Rahman Alhiti, Othman Farooq Bakr, Mudhafar A. Shafiq, Thamer Al-Hilfi, Salar Husein Karim
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Dzhumaeva Lazokatkhon

    Department of Anatomy, Histology and Normal Physiology, International Medical Faculty, Osh State University, Osh 723500, Kyrgyzstan
  • Hazim Abdul Rahman Alhiti

    Department of Medical Laboratory Analysis, Al Mansour University College, Baghdad 10067, Iraq
  • Othman Farooq Bakr

    Department of Medical Laboratory Analysis, Al-Turath University, Baghdad 10013, Iraq
  • Mudhafar A. Shafiq

    Department of Medical Laboratory Analysis, Al-Rafidain University College Baghdad 10064, Iraq
  • Thamer Al-Hilfi

    Department of Medical Laboratory Analysis, Madenat Alelem University College, Baghdad 10006, Iraq
  • Salar Husein Karim

    Department of Medical Laboratory Analysis, Chemical Weapon Victim’s Hospital, Halabja General Directorate of Health, Halabja 46018, Kurdistan Region, Iraq

Received: 15 February 2025; Revised: 14 March 2025; Accepted: 3 June 2025; Published: 14 November 2025

Considering what was said about Heat Shock Proteins (HSPs) role in the presentation of tumor antigens, today, before using tumor cell extracts as antigens in vaccine preparation, researchers try to increase the efficiency of antigen presentation by APCs via inducing these proteins; however, since different cell lines express different amounts of HSPs under the influence of different temperatures and different incubation times, discussing the optimal temperature and post-temperature incubation for cancer cell lines that may cause the next stages of the production of cancer cell vaccines, will be very useful. Through systematic search in PubMed/Medline using ("Tumor"[Title/Abstract] OR "Cancer"[Title/Abstract] OR "Neoplasm"[Title/Abstract]) AND ("vaccine"[Title/Abstract] OR "vaccination"[Title/Abstract]) AND ("heat shock protein"[Title/Abstract] OR "HSP"[Title/Abstract]) from 1980 to 2025. Overall, 18 articles were selected from a total of 414. The results of clinical trials confirm the use of HSPs in cancer vaccine therapy. A total of 18 studies, including 1,116 cases with different forms of cancer, were reviewed. These studies spanned different trial phases (I–III) and utilized a range of HSP-based vaccines to evaluate their safety, immunogenicity, and efficacy. HSPPC-96 was the most commonly investigated vaccine. These results indicate that the specific tumor-specific effects of the HSPs' immune response, including cluster of differentiation 4 (CD4+), interferon gamma (IFN-γ), and CD8+, lead to a much stronger vaccination. These outcomes underscore the complexity of the tumor microenvironment and the necessity for tailored approaches to maximize therapeutic success. Advances in vaccine formulation, production, and combination therapies offer promising pathways to address these challenges.

Keywords:

Heat Shock Proteins (HSPs) Immune Responses Immunotherapy Cancer Vaccine

References

  1. Guerrero Manriquez, G.G.; Tuero, I. Adjuvants: Friends in Vaccine Formulations Against Infectious Diseases. Hum. Vaccin. Immunother. 2021, 17, 3539–3550.
  2. Quintana, F.J.; Cohen, I.R. Heat Shock Proteins as Endogenous Adjuvants in Sterile and Septic Inflammation. J. Immunol. 2005, 175, 2777–2782.
  3. Kensil, C.; Mo, A.; Truneh, A. Current Vaccine Adjuvants: An Overview of a Diverse Class. Front. Biosci. 2004, 9, 2972–2988.
  4. Mengal, K.; Kor, G.; Kozák, P.; et al. Heat Shock Proteins Adaptive Responses to Environmental Stressors and Implications in Health Management of Decapods. Aquac. Rep. 2023, 30, 101564.
  5. Fulda, S.; Gorman, A.M.; Hori, O.; et al. Cellular Stress Responses: Cell Survival and Cell Death. Int. J. Cell Biol. 2010, 2010, 214074.
  6. Asea, A. Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72. Curr. Immunol. Rev. 2006, 2, 209–215.
  7. Park, C.J.; Seo, Y.S. Heat Shock Proteins: A Review of the Molecular Chaperones for Plant Immunity. Plant Pathol. J. 2015, 31, 323–333.
  8. Bakthisaran, R.; Tangirala, R.; Rao, C.M. Small Heat Shock Proteins: Role in Cellular Functions and Pathology. Biochim. Biophys. Acta Proteins Proteom. 2015, 1854, 291–319.
  9. Ranek, M.J.; Stachowski, M.J.; Kirk, J.A.; et al. The Role of Heat Shock Proteins and Co-Chaperones in Heart Failure. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2018, 373, 20160530.
  10. Binder, R.J. Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System. J. Immunol. 2014, 193, 5765–5771.
  11. Murshid, A.; Gong, J.; Calderwood, S.K. The Role of Heat Shock Proteins in Antigen Cross Presentation. Front. Immunol. 2012, 3, 63.
  12. Gaston, J.S. Heat Shock Proteins and Innate Immunity. Clin. Exp. Immunol. 2002, 127, 1–3.
  13. Rowles, J.E.; Keane, K.N.; Heck, T.G.; et al. Are Heat Shock Proteins an Important Link Between Type 2 Diabetes and Alzheimer Disease? Int. J. Mol. Sci. 2020, 21, 1–20.
  14. Leak, R.K. Heat Shock Proteins in Neurodegenerative Disorders and Aging. J. Cell Commun. Signal. 2014, 8, 293–310.
  15. Szyller, J.; Bil-Lula, I. Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits From Physical Exercises: A Review to the Current Knowledge. Oxid. Med. Cell. Longev. 2021, 2021, 6678457.
  16. Guo, J.; Chang, C.; Li, W. The Role of Secreted Heat Shock Protein-90 (Hsp90) in Wound Healing – How Could It Shape Future Therapeutics? Expert Rev. Proteomics 2017, 14, 665–675.
  17. Zügel, U.; Kaufmann, S.H. Role of Heat Shock Proteins in Protection From and Pathogenesis of Infectious Diseases. Clin. Microbiol. Rev. 1999, 12, 19–39.
  18. Mukherjee, A.G.; Wanjari, U.R.; Namachivayam, A.; et al. Role of Immune Cells and Receptors in Cancer Treatment: An Immunotherapeutic Approach. Vaccines 2022, 10, 1–24.
  19. Zhou, Q.; Guan, X.Y.; Li, Y. Roles of Heat Shock Proteins in Tumor Immune Microenvironment. Vaccines Cell. Mol. Med. 2024, 5, 3.
  20. Sastry, S.; Linderoth, N. Molecular Mechanisms of Peptide Loading by the Tumor Rejection Antigen/Heat Shock Chaperone gp96 (GRP94). J. Biol. Chem. 1999, 274, 12023–12035.
  21. Calderwood, S.K.; Theriault, J.R.; Gong, J. Message in a Bottle: Role of the 70-kDa Heat Shock Protein Family in Anti-Tumor Immunity. Cell Stress Chaperones 2005, 35, 2518–2527.
  22. Thériault, J.R.; Mambula, S.S.; Sawamura, T.; et al. Extracellular HSP70 Binding to Surface Receptors Present on Antigen Presenting Cells and Endothelial/Epithelial Cells. FEBS Lett. 2005, 579, 1951–1960.
  23. Stocki, P.; Wang, X.N.; Dickinson, A.M. Inducible Heat Shock Protein 70 Reduces T Cell Responses and Stimulatory Capacity of Monocyte-Derived Dendritic Cells. J. Biol. Chem. 2012, 287, 12387–12394.
  24. Liu, B.; DeFilippo, A.M.; Li, Z. Overcoming Immune Tolerance to Cancer by Heat Shock Protein Vaccines. Mol. Cancer Ther. 2002, 1, 1147–1151.
  25. Li, Y.; Subjeck, J.; Yang, G.; et al. Generation of Anti-Tumor Immunity Using Mammalian Heat Shock Protein 70 DNA Vaccines for Cancer Immunotherapy. Vaccine 2006, 24, 5360–5370.
  26. Callahan, M.K.; Chaillot, D.; Jacquin, C.; et al. Differential Acquisition of Antigenic Peptides by Hsp70 and Hsc70 Under Oxidative Conditions. J. Biol. Chem. 2002, 277, 33604–33609.
  27. Borges, T.J.; Wieten, L.; van Herwijnen, M.J.; et al. The Anti-Inflammatory Mechanisms of Hsp70. Front. Immunol. 2012, 3, 95.
  28. Campisi, J.; Leem, T.H.; Fleshner, M. Stress-Induced Extracellular Hsp72 Is a Functionally Significant Danger Signal to the Immune System. Cell Stress Chaperones 2003, 8, 272–286.
  29. Radons, J. The Human HSP70 Family of Chaperones: Where Do We Stand? Cell Stress Chaperones 2016, 21, 379–404.
  30. Yazdi, M.; Kafshgari, M.H.; Moghadam, F.K.; et al. Crosstalk Between NK Cell Receptors and Tumor Membrane Hsp70-Derived Peptide: A Combined Computational and Experimental Study. Adv. Sci. 2024, 11, 2305998.
  31. Guzhova, I.V.; Margulis, B.A. HSP70-Based Anti-Cancer Immunotherapy. Hum. Vaccin. Immunother. 2016, 12, 2529–2535.
  32. Verma, C.; Pawar, V.A.; Srivastava, S.; et al. Cancer Vaccines in the Immunotherapy Era: Promise and Potential. Vaccines 2023, 11, 1–19.
  33. Enokida, T.; Moreira, A.; Bhardwaj, N. Vaccines for Immunoprevention of Cancer. J. Clin. Investig. 2021, 131, e147147.
  34. Mehrizi, T.Z.; Ataei-Pirkooh, A.; Eshrati, B.; et al. Investigating Factors Affecting the Effectiveness of Gardasil 4, Cervarix, and Gardasil 9 Vaccines Considering the WHO Regions in Females: A Systematic Review. Cancer Epidemiol. 2025, 95, 102759.
  35. Zhao, Y.; Baldin, A.V.; Isayev, O.; et al. Cancer Vaccines: Antigen Selection Strategy. Vaccines 2021, 9, 1–12.
  36. Wu, Z.; Li, S.; Zhu, X. The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity. Front. Immunol. 2021, 12, 682435.
  37. Ruzzi, F.; Riccardo, F.; Conti, L.; et al. Cancer Vaccines: Target Antigens, Vaccine Platforms and Preclinical Models. Mol. Aspects Med. 2025, 101, 101324.
  38. de Gruijl, T.D.; van den Eertwegh, A.J.; Pinedo, H.M.; et al. Whole-Cell Cancer Vaccination: From Autologous to Allogeneic Tumor- and Dendritic Cell-Based Vaccines. Cancer Immunol. Immunother. 2008, 57, 1569–1577.
  39. Lee, K.W.; Yam, J.W.P.; Mao, X. Dendritic Cell Vaccines: A Shift From Conventional Approach to New Generations. Cells 2023, 12, 1–18.
  40. Larocca, C.; Schlom, J. Viral Vector-Based Therapeutic Cancer Vaccines. Cancer J. 2011, 17, 359–371.
  41. Sellers, R.S.; Nelson, K. Chapter 9 - Vaccines. In Haschek and Rousseaux's Handbook of Toxicologic Pathology, 4th ed.; Haschek, W.M., Rousseaux, C.G., Wallig, M.A., et al., Eds.; Academic Press: Cambridge, MA, USA, 2023; pp. 335–396.
  42. Kumar, V.; Roy, S.; Behera, B.K.; et al. Heat Shock Proteins (Hsps) in Cellular Homeostasis: A Promising Tool for Health Management in Crustacean Aquaculture. Life 2022, 12, 1748.
  43. DeNicola, D.M. 6 - Periphyton Responses to Temperature at Different Ecological Levels. In Algal Ecology; Stevenson, R.J., Bothwell, M.L., Lowe, R.L., Eds.; Academic Press: San Diego, CA, USA, 1996; pp. 149–181.
  44. Gao, G.; Liu, S.; Yao, Z.; et al. The Prognostic Significance of Hsp70 in Patients With Colorectal Cancer: A PRISMA-Compliant Meta-Analysis. Biomed. Res. Int. 2021, 2021, 5526327.
  45. Liu, C.C.; Jan, Y.J.; Ko, B.S.; et al. 14-3-3σ Induces Heat Shock Protein 70 Expression in Hepatocellular Carcinoma. BMC Cancer 2014, 14, 425.
  46. Feng, J.; Zhan, Y.; Zhang, Y.; et al. Increased Expression of Heat Shock Protein (HSP) 10 and HSP70 Correlates With Poor Prognosis of Nasopharyngeal Carcinoma. Cancer Manag. Res. 2019, 11, 8219–8227.
  47. Jagadish, N.; Agarwal, S.; Gupta, N.; et al. Heat Shock Protein 70-2 (HSP70-2) Overexpression in Breast Cancer. J. Exp. Clin. Cancer Res. 2016, 35, 150.
  48. Rothammer, A.; Sage, E.K.; Werner, C.; et al. Increased Heat Shock Protein 70 (Hsp70) Serum Levels and Low NK Cell Counts After Radiotherapy: Potential Markers for Predicting Breast Cancer Recurrence? Radiat. Oncol. 2019, 14, 78.
  49. Ciocca, D.R.; Clark, G.M.; Tandon, A.K.; et al. Heat Shock Protein Hsp70 in Patients With Axillary Lymph Node-Negative Breast Cancer: Prognostic Implications. J. Natl. Cancer Inst. 1993, 85, 570–574.
  50. Mahjabeen, I.; Sheshe, S.; Shakoor, T.; et al. Role of Genetic Variations of DNA Damage Response Pathway Genes and Heat-Shock Proteins in Increased Head and Neck Cancer Risk. Future Oncol. 2022, 18, 3519–3535.
  51. Gunaldi, M.; Afsar, C.U.; Okuturlar, Y.; et al. Elevated Serum Levels of Heat Shock Protein 70 Are Associated With Breast Cancer. Tohoku J. Exp. Med. 2015, 236, 97–102.
  52. Souza, A.P.; Albuquerque, C.; Torronteguy, C.; et al. HspBP1 Levels Are Elevated in Breast Tumor Tissue and Inversely Related to Tumor Aggressiveness. Cell Stress Chaperones 2009, 14, 301–310.
  53. de Freitas, G.B.; Penteado, L.; Miranda, M.M.; et al. The Circulating 70 kDa Heat Shock Protein (HSPA1A) Level Is a Potential Biomarker for Breast Carcinoma and Its Progression. Sci. Rep. 2022, 12, 13012.
  54. Davidoff, A.M.; Iglehart, J.D.; Marks, J.R. Immune Response to p53 Is Dependent Upon p53/HSP70 Complexes in Breast Cancers. Proc. Natl. Acad. Sci. USA 1992, 89, 3439–3442.
  55. Sobhani, N.; D’Angelo, A.; Wang, X.; et al. Mutant p53 as an Antigen in Cancer Immunotherapy. Cancers 2020, 21, 4087.
  56. Hu, S.; Arellano, M.; Boontheung, P.; et al. Salivary Proteomics for Oral Cancer Biomarker Discovery. Clin. Cancer Res. 2008, 14, 6246–6252.
  57. Motahari, P.; Zamiri, R.E.; Fatemi, M. Evaluation of Salivary Level of Heat Shock Protein 70 in Patients With Breast Cancer. Iran. J. Breast Dis. 2022, 14, 21–30.
  58. Bloch, O.; Crane, C.A.; Fuks, Y.; et al. Heat-Shock Protein Peptide Complex-96 Vaccination for Recurrent Glioblastoma: A Phase II, Single-Arm Trial. Neuro-Oncol. 2014, 16, 274–279.
  59. Bloch, O.; Lim, M.; Sughrue, M.E.; et al. Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy. Clin. Cancer Res. 2017, 23, 3575–3584.
  60. Ji, N.; Zhang, Y.; Liu, Y.; et al. Heat Shock Protein Peptide Complex-96 Vaccination for Newly Diagnosed Glioblastoma: A Phase I, Single-Arm Trial. JCI Insight. 2018, 3, e122229.
  61. Crane, C.A.; Han, S.J.; Ahn, B.; et al. Individual Patient-Specific Immunity Against High-Grade Glioma After Vaccination With Autologous Tumor Derived Peptides Bound to the 96 KD Chaperone Protein. Clin. Cancer Res. 2013, 19, 205–214.
  62. Pilla, L.; Patuzzo, R.; Rivoltini, L.; et al. A Phase II Trial of Vaccination With Autologous, Tumor-Derived Heat-Shock Protein Peptide Complexes Gp96, in Combination With GM-CSF and Interferon-Alpha in Metastatic Melanoma Patients. Cancer Immunol. Immunother. 2006, 55, 958–968.
  63. Testori, A.; Richards, J.; Whitman, E.; et al. Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein Gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group. J. Clin. Oncol. 2008, 26, 955–962.
  64. Wood, C.; Srivastava, P.; Bukowski, R.; et al. An Adjuvant Autologous Therapeutic Vaccine (HSPPC-96; Vitespen) Versus Observation Alone for Patients at High Risk of Recurrence After Nephrectomy for Renal Cell Carcinoma: A Multicentre, Open-Label, Randomised Phase III Trial. Lancet. 2008, 372, 145–154.
  65. Trimble, C.L.; Peng, S.; Kos, F.; et al. A Phase I Trial of a Human Papillomavirus DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3. Clin. Cancer Res. 2009, 15, 361–367.
  66. Shimizu, Y.; Yoshikawa, T.; Kojima, T.; et al. Heat Shock Protein 105 Peptide Vaccine Could Induce Antitumor Immune Reactions in a Phase I Clinical Trial. Cancer Sci. 2019, 110, 3049–3060.
  67. Van Doorslaer, K.; Reimers, L.L.; Studentsov, Y.Y.; et al. Serological Response to an HPV16 E7 Based Therapeutic Vaccine in Women With High-Grade Cervical Dysplasia. Gynecol. Oncol. 2010, 116, 208–212.
  68. Einstein, M.H.; Kadish, A.S.; Burk, R.D.; et al. Heat Shock Fusion Protein-Based Immunotherapy for Treatment of Cervical Intraepithelial Neoplasia III. Gynecol. Oncol. 2007, 106, 453–460.
  69. Victora, G.D.; Socorro-Silva, A.; Volsi, E.C.; et al. Immune Response to Vaccination With DNA-Hsp65 in a Phase I Clinical Trial With Head and Neck Cancer Patients. Cancer Gene Ther. 2009, 16, 598–608.
  70. Roman, L.D.; Wilczynski, S.; Muderspach, L.I.; et al. A Phase II Study of Hsp-7 (SGN-00101) in Women With High-Grade Cervical Intraepithelial Neoplasia. Gynecol. Oncol. 2007, 106, 558–566.
  71. Maki, R.G.; Livingston, P.O.; Lewis, J.J.; et al. A Phase I Pilot Study of Autologous Heat Shock Protein Vaccine HSPPC-96 in Patients With Resected Pancreatic Adenocarcinoma. Dig. Dis. Sci. 2007, 52, 1964–1972.
  72. Oki, Y.; McLaughlin, P.; Fayad, L.E.; et al. Experience With Heat Shock Protein-Peptide Complex 96 Vaccine Therapy in Patients With Indolent Non-Hodgkin Lymphoma. Cancer 2007, 109, 77–83.
  73. Palefsky, J.M.; Berry, J.M.; Jay, N.; et al. A Trial of SGN-00101 (HspE7) to Treat High-Grade Anal Intraepithelial Neoplasia in HIV-Positive Individuals. AIDS. 2006, 20, 1151–1155.
  74. Li, Z.; Qiao, Y.; Liu, B.; et al. Combination of Imatinib Mesylate With Autologous Leukocyte-Derived Heat Shock Protein and Chronic Myelogenous Leukemia. Clin. Cancer Res. 2005, 11, 4460–4468.
  75. Belli, F.; Testori, A.; Rivoltini, L.; et al. Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein Gp96-Peptide Complexes: Clinical and Immunologic Findings. J. Clin. Oncol. 2002, 20, 4169–4180.
  76. Shanmugam, A.; Suriano, R.; Goswami, N.; et al. Identification of Peptide Mimotopes of Gp96 Using Single-Chain Antibody Library. Cell Stress Chaperones. 2011, 16, 225–234.
  77. Wang, X.Y.; Sun, X.; Chen, X.; et al. Superior Antitumor Response Induced by Large Stress Protein Chaperoned Protein Antigen Compared With Peptide Antigen. J. Immunol. 2010, 184, 6309–6319.
  78. Massé, D.; Ebstein, F.; Bougras, G.; et al. Increased Expression of Inducible HSP70 in Apoptotic Cells Is Correlated With Their Efficacy for Antitumor Vaccine Therapy. Int. J. Cancer. 2004, 111, 575–583.
  79. Gong, J.; Zhang, Y.; Durfee, J.; et al. A Heat Shock Protein 70-Based Vaccine With Enhanced Immunogenicity for Clinical Use. J. Immunol. 2010, 184, 488–496.
  80. Enomoto, Y.; Bharti, A.; Khaleque, A.A.; et al. Enhanced Immunogenicity of Heat Shock Protein 70 Peptide Complexes From Dendritic Cell–Tumor Fusion Cells. J. Immunol. 2006, 177, 5946–5955.
  81. Kang, J.; Lee, H.J.; Lee, J.; et al. Novel Peptide-Based Vaccine Targeting Heat Shock Protein 90 Induces Effective Antitumor Immunity in a HER2+ Breast Cancer Murine Model. J. Immunother. Cancer 2022, 10, e004830.
  82. Stetler, R.A.; Gan, Y.; Zhang, W.; et al. Heat Shock Proteins: Cellular and Molecular Mechanisms in the Central Nervous System. Prog. Neurobiol. 2010, 92, 184–211.
  83. Nayak, D.A.; Binder, R.J. Agents of Cancer Immunosurveillance: HSPs and dsDNA. Trends Immunol. 2022, 43, 404–413.
  84. Pradeu, T.; Cooper, E.L. The Danger Theory: 20 Years Later. Front. Immunol. 2012, 3, 287.
  85. Santos, T.G.; Martins, V.R.; Hajj, G.N.M. Unconventional Secretion of Heat Shock Proteins in Cancer. Int. J. Mol. Sci. 2017, 18, 945.
  86. Milani, V.; Noessner, E.; Ghose, S.; et al. Heat Shock Protein 70: Role in Antigen Presentation and Immune Stimulation. Int. J. Hyperthermia 2002, 18, 563–575.
  87. Bastaki, N.K.; Albarjas, T.A.; Almoosa, F.A.; et al. Chronic Heat Stress Induces the Expression of HSP Genes in the Retina of Chickens (Gallus gallus). Front. Genet. 2023, 14, 1085590.
  88. Bendz, H.; Ruhland, S.C.; Pandya, M.J.; et al. Human Heat Shock Protein 70 Enhances Tumor Antigen Presentation Through Complex Formation and Intracellular Antigen Delivery Without Innate Immune Signaling. J. Biol. Chem. 2007, 282, 31688–31702.
  89. Horváth, I.; Multhoff, G.; Sonnleitner, A.; et al. Membrane-Associated Stress Proteins: More Than Simply Chaperones. Biochim. Biophys. Acta Biomembr. 2008, 1778, 1653–1664.
  90. Linderoth, N.A.; Popowicz, A.; Sastry, S. Identification of the Peptide-Binding Site in the Heat Shock Chaperone/Tumor Rejection Antigen gp96 (Grp94). J. Biol. Chem. 2000, 275, 5472–5477.
  91. Schueller, G.; Stift, A.; Friedl, J.; et al. Hyperthermia Improves Cellular Immune Response to Human Hepatocellular Carcinoma Subsequent to Co-Culture With Tumor Lysate Pulsed Dendritic Cells. Int. J. Oncol. 2003, 22, 1397–1402.
  92. Falahi, S.; Kenarkoohi, A. Host Factors and Vaccine Efficacy: Implications for COVID-19 Vaccines. J. Med. Virol. 2022, 94, 1330–1335.
  93. Singh, D.N.; Daripelli, S.; Bushara, M.O.E.; et al. Genetic Testing for Successful Cancer Treatment. Cureus 2023, 15, e49889.
  94. Coutinho, F.A.B.; Amaku, M.; Boulos, F.C.; et al. Analysing Vaccine Efficacy Evaluated in Phase 3 Clinical Trials Carried Out During Outbreaks. Infect. Dis. Model. 2024, 9, 1027–1044.
  95. Pollard, A.J.; Bijker, E.M. A Guide to Vaccinology: From Basic Principles to New Developments. Nat. Rev. Immunol. 2021, 21, 83–100.
  96. Corthay, A. Does the Immune System Naturally Protect Against Cancer? Front. Immunol. 2014, 5, 197.
  97. Yamaguchi, H.; Hiroi, M.; Mori, K.; et al. Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4(+), CD8(+), and Foxp3(+) Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis. Cancers 2021, 13, 1988.
  98. Kogame, M.; Nagai, H.; Shinohara, M.; et al. Th2 Dominance Might Induce Carcinogenesis in Patients With HCV-Related Liver Cirrhosis. Anticancer Res. 2016, 36, 4529–4536.
  99. Kany, S.; Vollrath, J.T.; Relja, B. Cytokines in Inflammatory Disease. Int. J. Mol. Sci. 2019, 20, 6008.
  100. Chen, L.; Deng, H.; Cui, H.; et al. Inflammatory Responses and Inflammation-Associated Diseases in Organs. Oncotarget 2018, 9, 7204–7218.
  101. Kiros, T.G.; Levast, B.; Auray, G.; et al. The Importance of Animal Models in the Development of Vaccines: Innovation in Vaccinology. In The Science and Practice of Vaccinology; Gerdts, V., Ed.; Springer: Dordrecht, Netherlands, 2012; pp. 251–264.
  102. Beheshtizadeh, N.; Gharibshahian, M.; Pazhouhnia, Z.; et al. Commercialization and Regulation of Regenerative Medicine Products: Promises, Advances and Challenges. Biomed. Pharmacother. 2022, 153, 113431.
  103. Sampathkumar, K.; Kerwin, B.A. Roadmap for Drug Product Development and Manufacturing of Biologics. J. Pharm. Sci. 2024, 113, 314–331.
  104. Srivastava, S.; Singh, D.; Verma, S.K.; et al. Recent Advancements in Cancer Vaccines: A Systematic Review. Vacunas 2024, 25, 97–108.
  105. Rulten, S.L.; Grose, R.P.; Gatz, S.A.; et al. The Future of Precision Oncology. Int. J. Mol. Sci. 2023, 24, 9110.
  106. Harrop, R. Cancer Vaccines: Identification of Biomarkers Predictive of Clinical Efficacy. Hum. Vaccines Immunother. 2013, 9, 800–804.
  107. Alum, E.U. AI-Driven Biomarker Discovery: Enhancing Precision in Cancer Diagnosis and Prognosis. Discov. Oncol. 2025, 16, 313.
  108. Passaro, A.; Al Bakir, M.; Hamilton, E.G.; et al. Cancer Biomarkers: Emerging Trends and Clinical Implications for Personalized Treatment. Cell 2024, 187, 1617–1635.

Copyright © UK Scientific Publishing Limited.