Prospective cancer vaccines for prevention and treatment of cancer

Jamila  Ali Hamed Alhoderi; Nelson  Fernandez

doi:10.51984/joms.v17i2.2187

Authors

Jamila Ali Hamed Alhoderi Sebha University, Sebha-Libya,
Nelson Fernandez Unversity of Essex, Colchester-UK

DOI:

https://doi.org/10.51984/joms.v17i2.2187

Keywords:

Cancer vaccines, Dendritic cells-based cancer, vaccines, Prophylactic cancer vaccines, Therapeutic cancer vaccines, Tumour immunology

Abstract

To study tumour immunity and vaccines, knowledge of tumour antigens and genes that encode them is essential. Cancer vaccines and cancer immunotherapy have been developed as a fourth type of treatment. There are two main categories of cancer vaccines: prophylactic (preventative) or therapeutic (curative). Prophylactic vaccines are given to healthy individuals whereas, therapeutic cancer vaccines are administered to cancer patients as a treatment, and the option of therapeutic vaccines is the personalized vaccines which are specific for tumour type and individual patient. The identification and characterization of tumour antigens that are highly immunogenic in human tumours are the key issue in tumour immunology. The candidate tumour antigen for cancer vaccine should have a potent effect in elicitation a specific humoral B cell and cellular T cell responses. To design cancer vaccines, it is necessary to identify a tumour antigen that can generate helper and cytotoxic T cells response and present tumour epitopes effectively. Several strategies have been developed to improve T cell-mediated immunotherapy and tumour vaccines. The current review highlights the tumour antigens as the main target for cancer vaccines; presentation of tumour antigens to CD4+ T cells, and strategies for cancer vaccines in terms of effectiveness of this treatment and the factors that affect the efficacy. Prophylactic, therapeutic, and personalized cancer vaccines have significant promise, but significant work remains to realize that potential. Therefore, technological advancements and a better understanding of tumour-host immune interactions are recommended to realize the mechanisms of resistance to the anti-tumour immune response.

Downloads

Download data is not yet available.

Author Biographies

Jamila Ali Hamed Alhoderi, Sebha University, Sebha-Libya,

Sebha University, Sebha-Libya,
Nelson Fernandez, Unversity of Essex, Colchester-UK

Unversity of Essex, Colchester-UK

References

[1]Robinson, J.H., Delvig, A. A., (2002), Diversity of MHC antigen presentation., Immunology., 105, 252-262. DOI: 10.1046/j.0019-2805.2001.01358.x.

[2]Chaplin, D.D., (2010), Overview of the Immune Response., J Allergy Clin Immunol., 125(Suppl 2), S3–23. DOI: 10.1016/j.jaci.2009.12.980.

[3]Graziano, D.F., Finn, O.J., (2005), Tumor Antigens and Tumor Antigen Discovery., Cancer. Treat. Res., 123, 89-111. DOI: 10.1007/0-387-27545-2_4

[4]T.J. Kindt, R.A. Goldsby, B. A Osborne, Kuby Immunology. 6th edition. W. H. Freeman and Company. USA, 2007, pp. 525-545.

[5]Finn, O.J., (2007), Human tumour immunology at the molecular divide., J. Immunol., 178, 2615-2616. DOI: 10.4049/jimmunol.178.5.2615.

[6]Bray, F. Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal A., (2018), Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries., CA Cancer J Clin., 68, 394-424. DOI: 10.3322/caac.21492.

[7]Igarashi, Y., Sasada, T., (2020), Cancer Vaccines: Toward the Next Breakthrough in Cancer Immunotherapy., J Immunol Res., 2020, 13 pages. DOI: 10.1155/2020/5825401.

[8]Donninger, H., Li C., Eaton, J. W., Yaddanapudi, K., (2021), Cancer Vaccines: Promising Therapeutics or an Unattainable Dream., Vaccines., 9, 668. DOI: 10.3390/vaccines9060668.

[9]Tay, B Q., Wright, Q., Ladwa, R., Perry, C., Leggatt, G., Simpson, F., Wells, J. W., Panizza, B. J., Frazer, I. H., Cruz, J. L. G., (2021), Evolution of Cancer Vaccines-Challenges, Achievements, and Future Directions. Vaccines., 9, 535. DOI: 10.3390/vaccines9050535.

[10]Antonarelli G., Corti C., Tarantino P., Ascione L., Cortes J., Romero P., Mittendorf E.A., Disis M.L., and Curigliano G. (2021). Therapeutic cancer vaccines revamping: technology advancements and pitfalls. Annals of Oncology 32 (12): 1537-1551. DOI: 10.1016/j.annonc.2021.08.2153.

[11]Vonderheide, R., Nathanson, K., (2013), Immunotherapy at Large: The road to personalized cancer vaccines., Nat Med., 19, 1098–1100. DOI: 10.1038/nm.3317.

[12]Zhang, X., Sharma, P.K., Goedegebuure, P. S., Gillanders, W.E., (2017), Personalized cancer vaccines: Targeting the cancer mutanome., Vaccine., 35, 1094-1100. DOI: 10.1038/nm.3317.

[13]Shemesh, C.S., Hsu, J.C., Hosseini, I., Shen, B.Q., Rotte, A., Twomey, P., Girish, S., Wu, B., (2021), Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities., Mol Ther., 29, 555-570. DOI: 10.1016/j.ymthe.2020.09.038.

[14]Fritah, H., Rovelli, R., Chiang, C. L-L., Kandalaft, L. E., (2022), The current clinical landscape of personalized cancer vaccines., Cancer Treatment Reviews., 106, 102383. DOI: 10.1016/j.ctrv.2022.102383.

[15]Guo, C., Manjili, M. H., Subjeck, J. R., Sarkar, D., Fisher, P. B., Wang X-Y., (2013), Therapeutic cancer vaccines: past, present, and future., Adv Cancer Res., 119, 421-75. DOI: 10.1016/B978-0-12-407190-2.00007-1.

[16]Hollingsworth, R.E., Jansen, K., (2019), Turning the corner on therapeutic cancer vaccines., npj Vaccines., 4, 7. DOI: 10.1038/s41541-019-0103-y.

[17]Parmiani, G., De Filippo, A., Novellino, l., Castelli, C. (2007). Unique human tumor antigens: Immunobiology and use in clinical trials. J. Immunol., 148, 975-1979. DOI: 10.4049/jimmunol.178.4.1975.

[18]Topalian, S.L., Gonzales, M., Parkhurst, M., ELi, Y., Southwood S., Sette, A., Rosenberg, S.A., Robbins, P.E., (1996), Melanoma-specific CD4+ T Cells Recognize Nonmutated HLA-DR-restricted Tyrosinase Epitopes., J. Exp. Med., 183, 1965-1971. DOI: 10.1084/JEM.183.5.1965.

[19]Gerloni M. and Zanetti, M. (2005). CD4 T cells in tumor immunity. Springer Semin Immun., 27, 37–48. DOI: 10.1007/s00281-004-0193-z.

[20]C. A. Janeway, P. Travers, M. Walport, M.J. Shlomchik, Immunobiology. 6th ediation. Garland Science Publishing. 2005.

[21]Paul, W.E., Seder, R.A., (1994), Lymphocyte responses and cytokines., Cell., 76, 241-251. DOI: 10.1016/0092-8674(94)90332-8.

[22]Ostrand-Rosenberg S (2005). CD4+ T lymphocytes: a critical component of antitumour immunity. Cancer Investigation 23: 413-419. DOI: 10.1081/CNV-67428.

[23]Tay R E., Richardson E K., Toh H C. (2021). Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms. Cancer Gene Therapy 28:5–17. DOI: 10.1038/s41417-020-0183-x.

[24]Ostrand-Rosenberg S. (2004). Animal models of tumour immunity, immunotherapy, and cancer vaccines. Curr Opin Immunol, 16, 143-150. DOI: 10.1016/j.coi.2004.01.003.

[25]Xu M., Qiu, G., Jiang, Z., von Hofe, E. and Humphreys, R.E. (2000). Genetic modulation of tumour antigen presentation. Trends Biotechnol, 18, 167-172. DOI: 10.1016/s0167-7799(00)01421-9.

[26]van der Bruggen P. and Van den Eynde, B.J. (2006). Processing and presentation of tumor antigens and vaccine strategies. Curr. Openi. Immunol., 18, 98-104. DOI: 10.1016/j.coi.2005.11.013.

[27]Qi L., Rojas, J´-M. and Ostrand-Rosenberg, S. (2000). Tumor Cells Present MHC Class II-Restricted Nuclear and Mitochondrial Antigens and Are the Predominant Antigen Presenting Cells In Vivo. J immunol, 164, 5451–5461. DOI: 10.4049/jimmunol.165.10.5451.

[28]Dissanayake S.K., Thompson, J.A., Bosch. JJ., Clements, VK., Chen P.W., Ksander, B.R. and Ostrand-Rosenberg, S. (2004). Activation of Tumor-specific CD4+ T Lymphocytes by Major Histocompatibility Complex Class II Tumor Cell Vaccines: A Novel Cell-based Immunotherapy. Cancer Research, 64, 1867–1874. DOI: 10.1158/0008-5472.can-03-2634.

[29]Henderson R.A. and Finn, O.J. (1996). Human Tumor Antigens Are Ready to Fly. Adv. Immunol., 62, 217-256. DOI: 10.1016/s0065-2776(08)60431-9.

[30]Berzofsky J A., Wood LV., Maeng H., Trepel J, Stroncek D., Morris J C. HER2 cancer vaccine phase I clinical trial shows clinical benefit in 54% of evaluable patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl): Abstract nr A004.

[31]Costa, R., Zaman, S., Sharpe, S., Helenowski, I., Shaw, C., Han, H., Soliman, H., & Czerniecki, B. (2019). A brief report of toxicity end points of HER2 vaccines for the treatment of patients with HER2+ breast cancer. Drug design, development, and therapy, 13, 309–316. DOI: 10.2147/DDDT.S188925.

[32]Pallerla S., Abdul A.M., Comeau J., and Jois S. (2021). Cancer Vaccines, Treatment of the Future: With Emphasis on HER2-Positive Breast Cancer. Int. J. Mol. Sci., 22(2), 779. DOI: 10.3390/ijms22020779.

[33]Corti C., Giachetti P.P.M.B., Eggermont A.M.A., Delaloge S., and Curigliano G. (2022). Therapeutic vaccines for breast cancer: Has the time finally come? European Journal of Cancer 160, 150-174. DOI: 10.1016/j.ejca.2021.10.027.

[34]Seliger B., Maeurer MJ and Ferrone S (2000). Antigen-processing machinery breakdown and tumor growth. Immunology Today 21(9):457-464. DOI: 10.1016/s0167-5699(00)01692-3.

[35]Dissanayake S.K., Tuera, N. and Ostrand-Rosenberg, S. (2005). Presentation of Endogenously Synthesized MHC Class II-Restricted Epitopes by MHC Class II Cancer Vaccines Is Independent of Transporter Associated with Ag Processing and the Proteasome. J Immunol, 174, 1811–1819. DOI: 10.4049/jimmunol.174.4.1811.

[36]Dolan B.P., Phelan, T.P., Ilkovitch, D., Qi, L., Wade, W.F., Laufer, T. M. and Ostrand-Rosenberg, S. (2004). Invariant Chain and the MHC Class II Cytoplasmic Domains Regulate Localization of MHC Class II Molecules to Lipid Rafts in Tumor Cell-Based Vaccines. J Immunol, 172, 907–914. DOI: 10.4049/jimmunol.172.2.907.

[37]Hiltbold E M and Roche PA (2002). Trafficking of MHC class II molecules in the late secretory pathway. Current Opinion in Immunology, 14, 30-35. DOI: 10.1016/s0952-7915(01)00295-3.

[38]Beswick, E. J., Reyes, V. E., (2009), CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract., World J Gastroentero., 15, 2855-61. DOI: 10.3748/wjg.15.2855.

[39]Qi, L., Ostrand-Rosenberg, S., (2000), MHC Class II presentation of endogenous tumor antigen by cellular vaccines depends on the endocytic pathway but not H2-M., Traffic., 1, 152–160. DOI: 10.1034/j.1600-0854.2000.010207.x.

[40]Zhao, Y., Boczkowski, D., Nair, S.K., Gilboa, E., (2003), Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity., Blood., 102, 4137-4142. DOI: 10.1182/blood-2003-06-1867.

[41]van Luijn, M.M., Chamuleau, M.E.D., Thompson, J.A., Ostrand-Rosenberg, S., Westers, T.M., Souwer, Y., Ossenkoppele, G.J., van Ham, S.M., van de Loosdrecht, A.A., (2010), Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4+ T-cell responses. Haematologica., 95, 485-493. DOI: 10.3324/haematol.2009.010595.

[42]Al Saadh, H., Spencer, P. S., Alabdulmenaim, W., Alghamdi, R., Madar, I. H., Miranda-Sayago, J. M., Fernández, N., (2017), Measurements of heterotypic associations between cluster of differentiation CD74 and CD44 in human breast cancer-derived cells., Oncotarget., 8, 92143–92156. DOI: 10.18632/oncotarget.20922.

[43]Al Saadh, H., Al Abdulmonem, W., Rasheed, Z., Madar, I.H., Alhoderi, J., Nasr Eldeen, S.K., Alradhwan, A., Alasmael, N., Alkhamiss, A., Fernández, N., (2019), Knockdown of CD-74 in the proliferative and apoptotic activity of breast cancer cells., Open Access Macedonian Journal of Medical Sciences., 7, 3169. DOI: 10.3889/oamjms.2019.354.

[44]Burton, J.D., Ely, S., Reddy, P.K., Stein, R., Gold, V., Cardillo, M., Goldenberg, M., (2004), CD74 Is Expressed by Multiple Myeloma and Is a Promising Target for Therapy., Clinical Cancer Research., 10, 6606–6611. DOI: 10.1158/1078-0432.CCR-04-0182.

[45]Singh-Jasuja, H., Emmerich, N.P.N., Rammensee, H.G., (2004), The Tübingen approach: identification, selection, and validation of tumor-associated HLA peptides for cancer therapy., Cancer Immunol Immunother., 53, 187–195. DOI: 10.1007/s00262-003-0480-x.

[46]Li, G., Miles, A., Line, A. et al., (2004), Identification of tumour antigens by serological analysis of cDNA expression cloning., Cancer Immunol Immunother., 53, 139–143. DOI: 10.1007/s00262-003-0471-y

[47]van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., Boon, T., (1991). A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma., Science., 254, 1643–1647. DOI: 10.1126/science.1840703.

[48]Scanlan, M.J., Gure, A.O., Jungbluth, A.A., Old, L.J., Chen, Y-T., (2002), Cancer/testis antigens: an expanding family of targets for cancer immunotherapy., Immunological Reviews, 188, 22–32. DOI: 10.1034/j.1600-065x.2002.18803.x.

[49]Scanlan, M.J., Simpson, A.J.G., Old, L.J., (2004), The cancer/testis genes: Review, standardization, and commentary., Cancer Immunity, 4, 1. PMID: 14738373.

[50]Boel, P., Wildmann, C., Sensi, M.L., Brasseur, R., Renauld, J.-C., Coulie, P., Boon, T., van der Bruggen, P., (1995), BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes., Immunity, 2, 167–175. DOI: 10.1016/s1074-7613(95)80053-0.

[51]De Backer, O., et al., (1999). Characterization of the GAGE genes that are expressed in various human cancers and in normal testis., Cancer Res, 59, 3157–3165. PMID: 10397259.

[52]Fratta, E., Coral, S., Covre, A., Parisi, G., Colizzi, F., Danielli, R., Nicolay, H. J. M., Sigalotti, L., Maio, M., (2011), The biology of cancer testis antigens: Putative function, regulation, and therapeutic potential., Molecular Oncology., 5, 164-182. DOI: 10.1016/j.molonc.2011.02.001.

[53]Sugita Y, Wada H, Fujita S, et al. (2004). NY-ESO-1 Expression and Immunogenicity in Malignant and Benign Breast Tumors., Cancer Res, 64, 2199-2204. DOI: 10.1158/0008-5472.CAN-03-3070.

[54]Jungbluth AA, Busam KJ, Kolb D, Iversen K, Coplan K, Chen Y-T, Spagnoli GC and Old LJ., (2000). Expression of MAGE-antigens in normal tissues and cancer. Int. J. Cancer, 85, 460–465. PMID: 10699915.

[55]Jones TA, Ogunkolade BW, Szary J, Aarum J, Mumin MA, Patel S, Pieri CA, and Sheer D (2011). Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells. PLoS ONE, 6, e22399. DOI: 10.1371/journal.pone.0022399.

[56]Loukinov D., Ghochikyan A., Mkrtichyan M., Ichim TE., Lobanenkov VV., Cribbs DH., and Agadjanyan MG. (2006). Antitumor Efficacy of DNA Vaccination to the Epigenetically Acting Tumor Promoting Transcription Factor BORIS and CD80 Molecular Adjuvant. Journal of Cellular Biochemistry 98, 1037–1043. DOI: 10.1002/jcb.20953.

[57]Gnjatic S et al., (2006). NY-ESO-1: Review of an immunogenic tumour antigen. Advances in Cancer Research, 95, 1-30. DOI: 10.1016/S0065-230X(06)95001-5.

[58]McCarthy E F. (2006). The Toxins of William B. Coley and the Treatment of Bone and Soft-Tissue Sarcomas. The Iowa Orthopaedic Journal, 26, 154-158.

[59]Rappuoli, R., (2007). Bridging the knowledge gaps in vaccine design. Nature Biotechnology, 25, 1361-1366. PMID: 16789469.

[60]Akewanlop, C., Watanabe, M., Singh, B., Walker, M., Kufe, D.W. and Hayes, D. F. (2001). Phagocytosis of Breast Cancer Cells Mediated by Anti-MUC-1 Monoclonal Antibody, DF3, and Its Bispecific Antibody. Cancer Research, 61, 4061–4065. PMID: 11358826.

[61]Farzand S, Siddique T, Saba K, Bukhari MH. Frequency of HER2/neu overexpression in adenocarcinoma of the gastrointestinal system. World J Gastroenterol. 2014 May 21;20(19):5889-96. PMID: 11358826.

[62]Jafri A, Rizvi S. (2017). Frequency of Her2/Neu Protein Expression in Ovarian Epithelial Cancers. J Coll Physicians Surg Pak. 27(9):544-546. PMID: 29017668.

[63]Wang D, Zhu H, Ye Q, Wang C, Xu Y. Prognostic Value of KIF2A and HER2-Neu Overexpression in Patients with Epithelial Ovarian Cancer. Medicine (Baltimore). 2016 Feb;95(8): e2803. PMID: 26937910.

[64]Hechtman JF, Polydorides AD. HER2/neu gene amplification and protein overexpression in gastric and gastroesophageal junction adenocarcinoma: a review of histopathology, diagnostic testing, and clinical implications. Arch Pathol Lab Med. 2012 Jun;136(6):691-7. DOI: 10.5858/arpa.2011-0168-RS.

[65]Eissa S., Ali H S., Al Tonsi A H., Zaglol A., El Ahmady O. (2005). HER2/neu expression in bladder cancer: relationship to cell cycle kinetics. Clin Biochem, 38, 142-8. DOI: 10.1016/j.clinbiochem.2004.09.004.

[66]Wang P., Munger, C.M., Joshi, A.D., Pirruccello, S.J., Joshi, S.S. (2004). Cytotoxicity of Cord Blood Derived Her2/neu-specific Cytotoxic T Lymphocytes against Human Breast Cancer in vitro and in vivo. Breast Cancer Research and Treatment, 83, 15-23. DOI: 10.1023/B:BREA.0000010688.55353.a8.

[67]Gall V A., Philips AV., Qiao N., Clise-Dwyer K., Perakis A A., Zhang M., Clifton GT., Sukhumalchandra P., Ma Q., Reddy SM., Yu D., Molldrem J J., Peoples GE., Alatrash G., (2017). Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells. Cancer Res., 77, 5374-5383. DOI: 10.1158/0008-5472.CAN-16-2774.

[68]Alhoderi J and Fernandez N, (2019). Dendritic cells as a model of a cell-based cancer vaccine for breast tumour. Breast Cancer Research Conference - Abstracts. 13-15/ December. Tripoli. Libya.

[69]Kim TS., Chopra A., O-Sullivan IS and Cohen EP (2006). Enhanced Immunity to Breast Cancer in Mice Immunized with Fibroblasts Transfected with a Complementary DNA Expression Library from Breast Cancer Cells: Enrichment of the Vaccine for Immunotherapeutic Cells. Journal of Immunotherapy, 29, 261-273. DOI: 10.1097/01.cji.0000197097.46100.bb.

[70]Criscitiello C. (2012). Tumor-associated antigens in breast cancer. Breast Care 7(4):262-6. DOI: 10.1159/000342164.

[71]Maraskovsky E., Slolander, S., Drane, DP., Schnurr, M., Le, TTT., Mateo, L., Luft, T., Masterman, K-A., Tai, T-Y., Chen, Q., Green, S., Slolander, A., Pearse, MJ., Lemonnier, FA., Chen, W., Cebon, J, and Suhrbier, A. (2004). NY-ESO-1 protein formulated in ISCOMATRIX adjuvant is a potent anticancer vaccine inducing both humoral and CD8+ T-cell-mediated immunity and protection against NY-ESO-1+ tumours. Clinical Cancer Research, 10, 2879-2890. DOI: 10.1158/1078-0432.ccr-03-0245.

[72]Jäger E, Karbach J, Gnjatic S, et al., (2006). Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. PNAS, 103, 14453–14458. DOI: 10.1073/pnas.0606512103.

[73]Valmori D, Souleimanian NE, Tosello V, et al., (2007). Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. PNAS, 104, 8947–8952. DOI: 10.1073/pnas.0703395104.

[74]Adams S, O’Neill DW, Nonaka D, et al., (2008). Immunization of Malignant Melanoma Patients with Full-Length NY-ESO-1 Protein Using TLR7 Agonist Imiquimod as Vaccine Adjuvant. The Journal of Immunology, 181, 776–784. DOI: 10.4049/jimmunol.181.1.776.

[75]Bioley G, Guillaume P, Luescher I, et al., (2009). HLA Class I-Associated Immunodominance Affects CTL Responsiveness to an ESO Recombinant Protein Tumour Antigen Vaccine. Clin Cancer Res, 15, 299-306. DOI: 10.1158/1078-0432.CCR-08-1747.

[76]Odunsi K., Qian, F., Matsuzaki, J., Mhawech-Fauceglia, P., Andrews, C., Hoffman, EW., Pan, L., Ritter, G., Villelia, J., Thomas, B., Rodabaugh, K., Lele, S., Shrikant, P., Old, LJ and Gnjatic, S. (2007). Vaccination with an NY-ESO-1 peptide of HLA class I/II specificity induces integrated humoral and T cell responses in ovarian cancer. PNAS, 104, 12837-12842. DOI: 10.1073/pnas.0703342104.

[77]Diefenbach CSM, Gnjatic S, Sabbatini P, et al., (2008). Safety and Immunogenicity Study of NY-ESO-1b Peptide and Montanide ISA-51 Vaccination of Patients with Epithelial Ovarian Cancer in High-Risk First Remission. Clin Cancer Res, 14, 2740-48. DOI: 10.1158/1078-0432.CCR-07-4619.

[78]Ayyoub M, Pignon P, Dojcinovic D, Raimbaud I, Old LJ, Luescher I, and Valmori D. (2010). Assessment of Vaccine-Induced CD4 T Cell Responses to the 119-143 Immunodominant Region of the Tumor-Specific Antigen NY-ESO-1 Using DRB1*0101 Tetramers. Clin Cancer Res, 16, 4607–15. DOI: 10.1158/1078-0432.ccr-10-1485.

[79]Ghochikyan A., Mkrtichyan M., Loukinov D., Mamikonyan G., Pack SD., Movsesyan N., Ichim TE., Cribbs DH., Lobanenkov VV and Agadjanyan MG. (2007). Elicitation of T Cell Responses to Histologically Unrelated Tumors by Immunization with the Novel Cancer-Testis Antigen, Brother of the Regulator of Imprinted Sites. The Journal of Immunology 178, 566–573. DOI: 10.4049/jimmunol.178.1.566.

[80]Qiu G., Goodchild, J., Humphreys, R.E. and Xu, M. (1999). Cancer immunotherapy by antisense suppression of Ii protein in MHC-class-II-positive tumour cells. Cancer Immunol, Immunother, 48, 499–506. DOI: 10.1007/s002620050598.

[81]Boczkowski D., Nair, SK., Nam, J-H., Lyerly, H.K. and Gilboa, E. (2000). Induction of Tumor Immunity and Cytotoxic T Lymphocyte Responses Using Dendritic Cells Transfected with Messenger RNA Amplified from Tumor Cells. Cancer Research, 60, 1028–1034. PMID: 10706120.

[82]Basu A., Ramamoorthi G., Jia Y., Faughn J., Wiener D., Awshah S., Kodumudi K., Czerniecki B J. (2019). Immunotherapy in breast cancer: Current status and future directions. Advances in Cancer Research, 143, 295-349. DOI: 10.1016/bs.acr.2019.03.006.

[83]Banchereau J and Palucka, A K. (2005). Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol, 5(4):296-306. DOI: 10.1038/nri1592.

[84]Mkrtichyan M, Ghochikyan A, Davtyan H, et al., (2011). Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cell Immunol, 270, 188–97. DOI: 10.1016/j.cellimm.2011.05.007

[85]www.immunospot.com; Cellular Technology Limited (CTL).

[86]Hunder N N., Wallen H., Cao J., Hendricks DW., Reilly JZ., Rodmyre R., Jungbluth A., Gnjatic S., Thompson JA, and Yee C. (2008). Treatment of metastatic with autologous CD4+ T cells against NY-ESO-1. NEJM, 358, 2698-2703. DOI: 10.1056/NEJMoa0800251.

[87]Jackson H., Dimopoulos N., Mifsud NA., Tai TY., Chen Q., Svobodova S., Browning J., Luescher I., Stockert L., Old LJ., Davis ID., Cebon J., and Chen W. (2006). Striking immunodominance hierarchy of naturally occurring CD8+ and CD4+ T cell responses to tumour antigen NY-ESO-1. The Journal of Immunology, 176, 5908-17. DOI: 10.4049/jimmunol.176.10.5908.

[88]Batchu RB., Moreno AM., Szmania SM., Bennett G., Spagnoli GC., Ponnazhagan S., Barlogie B., Tricot G., and van Rhee F (2005). Protein transduction of Dendritic cells for NY-ESO-1-based immunotherapy of myeloma. Cancer Res, 65, 10041-9. DOI: 10.1158/0008-5472.CAN-05-1383.

[89]Gnjatic, S., Atanackovic, D., Jager, E., Matsuo, M., Selvakumar, A., Altorki, NK, Maki, RG, Dupont, B., Ritter G., Chen, Y-T, Knuth, A., and Old LJ. (2003). Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses. PNAS, 100, 8862–8867. DOI: 10.1073/pnas.1133324100.

[90]Aurisicchio L. and Ciliberto G. (2012). Genetic cancer vaccines: current status and perspectives. Expert Opinion on Biological Therapy, 12(8), 1043-1058. DOI: 10.1517/14712598.2012.689279.

[91]Mkrtichyan M, Ghochikyan A, Loukinov D, Davtyan H, Ichim TE, Cribbs DH., Lobanenkov VV and Agadjanyan MG. (2008). DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumour growth and prolongs the survival of mice. Gene Therapy 15, 61–64. DOI: 10.1038/sj.gt.3303044.

[92]Gnjatic S, Altorki NK, NgTang D, et al., (2009). NY-ESO-1 DNA Vaccine Induces T-Cell Responses That Are Suppressed by Regulatory T Cells. Cancer Res, 15, 2130-39. DOI: 10.1158/1078-0432.CCR-08-2632.

[93]Cheever MA, Higano CS. (2011). PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 17(11):3520-6. DOI: 10.1158/1078-0432.CCR-10-3126.

[94]Seelig A. (2020). P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers. Front. Oncol., 10, Article 576559. DOI: 10.3389/fonc.2020.576559.

[95]Fan Y, Moon JJ. (2015). Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy. Vaccines 3(3):662-685. DOI: 10.3390/vaccines3030662.

[96]Riley, R.S., June, C.H., Langer, R. et al. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov 18, 175–196 (2019). DOI: 10.1038/s41573-018-0006-z.

[97]Zhang H and Chen J. (2018). Current status and future directions of cancer immunotherapy. J Cancer 9(10): 1773–1781. DOI: 10.7150/jca.24577.