Immune System Regulation With Cancer Vaccines Based on Dendritic Cells

 
 
International Journal of Biotech Trends and Technology (IJBTT)
 
© 2019 by IJBTT Journal
Volume - 9 Issue - 4                          
Year of Publication : 2019
Authors : Ruchika, Madhu Parmar, Vinod Kumar Gupta
DOI :  10.14445/22490183/IJBTT-V9I4P609

Citation

MLA Style:Ruchika, Madhu Parmar, Vinod Kumar Gupta.  Immune System Regulation With Cancer Vaccines Based on Dendritic Cells International Journal of Biotech Trends and Technology 9.4 (2019): 59-67.

APA Style:Ruchika, Madhu Parmar, Vinod Kumar Gupta(2019). Immune System Regulation With Cancer Vaccines Based on Dendritic Cells  International Journal of Biotech Trends and Technology, 9(4),59-67.

Abstract

The interplay between host immunity and tumor cells has opened the possibility of targeting tumor cells by modulation of the human immune system. Dendritic cells initiate and regulate T-cell immunity and are thus the key to optimization of all types of vaccines. DC biology insights offer a variety of opportunities to improve immunogenicity. Cancer immunotherapy involves the treatment of a tumor by utilizing the recombinant human immune system components to target the pro-tumor micro-environment or by revitalizing the immune system with the ability to ill tumor antigens. In this review, current immunotherapy approaches to cancer with special forms on dendritic cells based cancer vaccines and some recent development and findings for the clinical development of cancer vaccines are discussed.

References

[1] L. Gross, “Intradermal immunization of C3H mice against a sarcoma that originated in an animal of the same line”, Cancer Res., vol. 3, pp. 326–333, 1943.
[2] M. Girardi, D. E. Oppenheim, C. R. Steele, J. M. Lewis, E. Glusac, R. Filler, et al., “Regulation of cutaneous malignancy by gamma delta T cells”, Science, vol. 294, pp. 605–609, 2001.
[3] M. Girardi, E. Glusac, R. B. Filler, S. J. Roberts, I. Propperova, J. Lewis,et al., “The distinct contributions of murine T cell receptor TCRgammadelta+ and TCRalphabeta+ T cells to different stages of chemically induced skin cancer”, J. Exp. Med., vol. 198, pp. 747–755, 2003.
[4] Y. Gao, W. Yang, M. Pan, E. Scully, M. Girardi, L. H. Augenlicht, et al., “Gamma delta T cells provide an early source of interferon gamma in tumor immunity”, J. Exp. Med., vol. 198, pp. 433–442, 2003.
[5] M. E. van den Broek, D. Kagi, F. Ossendorp, R. Toes, S. Vamvakas, W. K. Lutz, et al., “Decreased tumor surveillance in perforin deficient mice, J. Exp. Med., vol. 184, pp. 1781–1790, 1996.
[6] M. J. Smyth, K. Takeda, Y. Hayakawa, J. J. Peschon, M. R. van den Brinkand H. Yagita,“Nature`s TRAIL–on a path to cancer immunotherapy”, Immunity, vol. 18, pp. 1–6, 2003.
[7] A. M. Barfoed, T. R. Petersen, A. F. Kirkin, P. Thor Straten, M. H. Claesson and J. Zeuthen, “Cytotoxic T-lymphocyte clones, established by stimulation with the HLA-A2 binding p5365-73 wild type peptide loaded on dendritic cells In vitro, specifically recognize and lyse HLA-A2 tumour cells overexpressing thep53 protein”,Scand. J. Immunol.,vol. 51,pp. 128–133, 2000.
[8] N. Vigneron, “Human tumor antigens and cancer immunotherapy” Biomed. Res. Int., vol. 948501, 2015.
[9] Bauer, V. Groh, J. Wu, A. Steinle, J. H. Phillips, L. L. Lanier, et al., “Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA”, Science, vol. 285, pp. 727–729, 1999.
[10] Shi, G. J. Tricot, T. K. Garg, P. A. Malaviarachchi, S. M. Szmania, R, E. Kellum, et al., “Bortezomib down-regulates the cell surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma”, Blood, vol. 111, pp. 1309–1317, 2008.
[11] G. M. Marincola, E. M. Jaffee, D. J. Hicklin and S. Ferrone, “Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance”,Adv. Immunol., vol. 74, pp. 181–273, 2000.
[12] H. T. Khong and N. P. Restifo, “Natural selection of tumor variants in the generation of "tumor escape" phenotypes”, Nat. Immunol., vol.3, pp. 999–1005, 2002.
[13] C. Uyttenhove, L. Pilotte, I. Theate, V. Stroobant, D. Colau, N. Parmentier, et al., “Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine2,3-dioxygenase”, Nat. Med., vol. 9, pp. 1269–1274, 2003.
[14] N. Rubinstein, M. Alvarez, N. W. Zwirner, M. A. Toscano, J. M. Ilarregui, A. Bravo, et al., “Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; a potential mechanism of tumor-immune privilege”, Cancer Cell, vol.5, pp. 241–251, 2004.
[15] J. M. Fauci, J. M. Straughn Jr, S. Ferrone and D. J. Buchsbaum, “A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer.Gynecol”, Oncol., vol. 127, pp. 420–425, 2012.
[16] G. B. da Silva, T. G. Silva, R. A. Duarte, N. L. Neto, H. H. Carrara, E. A. Donadi, et al., “Expression of the classical and nonclassical HLA molecules in breast cancer”, Int. J. Breast Cancer, vol. 25, pp. 04-35, 2013.
[17] N. Terabe and J. A. Berzofsky, “Immunoregulatory T cells in tumor immunity”, Curr. Opin. Immunol., vol. 16, pp. 157–162, 2004.
[18] M. Pardoll, “The blockade of immune checkpoints in cancer immunotherapy”, Nat. Rev. Cancer, vol. 12, pp. 252–264, 2012.
[19] M. Danielle, Lussier and D. Robert Schreiber, “Cancer Immunosurveillance: Immunoediting”,Refer. Mod. Biomed. Sciences, vol. 4, pp. 396-405, 2016.
[20] F. Granucci, M. Foti, P. R. Castagnoli, “Dendritic cell biology”, Adv. Immunol., vol. 88, pp. 193-233, 2005.
[21] J. W. Yewdell, C. C. Norbury and J. R. Bennink, “Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: implications for generating CD8+ T cell responses to infectious agents, tumors, transplants, and vaccines”, Adv. Immunol., vol. 73, pp. 1–77, 1999.
[22] L. H. Stockwin, D. McGonagle, I. G. Martin and G. E. Blair,“Dendritic cells: immunological sentinels with a central role in health and disease”, Immunol. Cell Biol., vol. 78, pp. 91–102, 2000.
[23] P. Guermonprez, J. Valladeau, L. Zitvogel, C. Thery and S. Amigorena, “Antigen presentation and T cell stimulation by dendritic cell”, Annu. Rev. Immunol., vol. 20, pp. 621–667, 2002.
[24] D. Pennock, J. T. White, E. W. Cross, E. E. Cheney, B. A. Tamburini and R. M. Kedl, “T cell responses: naive to memory and everything in between”,Adv. Physiol. Educ., vol. 37, pp. 273–283, 2013.
[25] M. Wykes and G. MacPherson, “Dendritic cell-B-cell interaction:dendritic cells provide B cells with CD40-independentproliferation signals and CD40-dependent survival signals”, Immunology, vol. 100, pp. 1–3, 2000.
[26] D. W. O`Neill, S. Adams and N. Bhardwaj, “Manipulating dendritic cell biology for the active immunotherapy of cancer”, Blood, vol. 104, pp. 2235–2246, 2004.
[27] C. Ardavin, S. Amigorenas and C. Sousa, “Dendritic cells: immunobiology and cancer immunotherapy”, Immunity, vol.20, pp. 17-23, 2004.
[28] A. Corthay, D. K. Skovseth, K. U. Lundin, E. Rosjo, H. Omholt, P. O. Hofgaard, et al., “Primary antitumor immune response mediated by CD4+ T cells”, Immunity, vol. 22, pp. 371–383, 2005
[29] R. Syme and S. Gluck, J Hematother., “Effects of cytokines on the culture and differentiation of dendritic cells in vitro”, J. Hematother. Stem Cell Res., vol.10, pp. 43–51, 2001.
[30] K. Chaitanya, K. Sakshi, et al., “Immune modulation by dendritic-cell-based cancer vaccines”, J. Biosci., vol. 42, pp. 161-173, 2017.
[31] Jeanbart and M. A. Swartz,“Engineering opportunities in cancer immunotherapy”,Proc. Natl. Acad. Sci. USA,vol. 112, pp. 14467–14472, 2015.
[32] Mellman, G. Coukos and G. Dranoff, “Cancer immunotherapy comes of age”, Nature, vol. 480,pp. 480–489, 2011.
[33] M. E. Dudley, J. R. Wunderlich, P. F. Robbins, J. C. Yang, P. Hwu, D. J. Schwartzentruber, et al., “Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes”, Science, vol. 298, pp. 850–854, 2002.
[34] S. Stevanovic, L. M. Draper, M. M. Langhan, T. E. Campbell, M. L. Kwong, J. R. Wunderlich, et al., “Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells”, J. Clin.Oncol., vol. 33, pp. 1543–1550, 2015.
[35] V. Velcheti and K. Schalper, “Basic Overview of Current Immunotherapy Approaches in Cancer,” Amer. Soci. Clin. Oncol., vol. 36, pp. 298-308, 2018.
[36] C. J. Voskens, S. M. Goldinger, C. Loquai, C. Robert, K. C. Kaehler, C. Berking, et al., “The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network, PLoS One, vol. 8, pp. e53745, 2013.
[37] G. R. Weiss, W. W. Grosh, K. A. Chianese-Bullock, Y. Zhao, H. Liu, C. L. Jr Slingluff, et al., “Molecular insights on the peripheral and intratumoral effects of systemic high-dose rIL-2(aldesleukin) administration for the treatment of metastatic melanoma”, Clin. Cancer Res., vol. 17, pp. 7440–7450, 2011.
[38] S. A. Rosenberg, P. Spiess, R. Lafreniere, et al., “A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes”, Science, vol. 19, pp. 233, 1986.
[39] C. Chester, O. Dorigo, J. S. Berek and H. Kohrt, “Immunotherapeutic approaches to ovarian cancer treatment”, J. Immunother. Cancer, vol. 3, pp. 7, 2015.
[40] M. Boland and Wen Wee Ma, “Immunotherapy of colorectal cancer”, Cancers (Basel), vol. 9, pp. 50, 2017.
[41] Bonini and A. Mondino, “Adoptive T-cell therapy for cancer:the era of engineered T cells”, Eur. J. Immunol, vol. 45, pp. 2457–2469, 2015.
[42] F. Ciceri, C. Bonini, M. T. Stanghellini, A. Bondanza, C. Traversari, M. Salomoni, et al., “Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): anon randomised phase I-II study”, Lancet Oncol., vol. 10, pp. 489–500, 2009.
[43] J. N. Brudno, R. P. Somerville, V. Shi, J. J. Rose, D. C. Halverson, D. H. Fowler, et al., “Allogeneic T cells that express an anti-CD19chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease”, J. Clin.Oncol., vol. 34, pp. 1112–1121, 2016.
[44] B. Mukherji, N. G. Chakraborty, S. Yamasaki, T. Okino, H. Yamase, J. R. Sporn, et al., “Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells”, Proc. Natl. Acad. Sci. USA, vol. 92, pp. 8078–8082, 1995.
[45] K. Palucka and J. Banchereau,“Cancer immunotherapy via dendritic cells”, Nat. Rev. Cancer, vol. 12, pp. 265–277, 2012.
[46] E. H. Aarntzen , C. G. Figdor, G. J. Adema, C. J. Punt, I. J. de Vries, “Dendritic cell vaccination and immune monitoring”, Cancer Immunol. Immunother., vol. 57, pp. 1559–1568, 2008.
[47] P. Kalinski, R. Muthuswamy, J. Urban, “Dendritic cells in cancer immunotherapy: vaccines and combination immunotherapies”, Expert Rev. Vaccines, vol. 12, pp. 285-295, 2013.
[48] G. Schuler, “Dendritic cells in cancer immunotherapy”, Eur. J. Immunol., vol. 40, pp. 2123-2130, 2010.
[49] C. Dieu, B. Vanbervliet, A. Vicari, J. M. Bridon, E. Oldham, S. Ait-Yahia, et al., “Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites”, J. Exp. Med., vol. 188, pp. 373–386, 1998.
[50] S. Yanagihara, E. Komura, J. Nagafune, H. Watarai and Y. Yamaguchi, “EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation”, J. Immunol., vol. 161, pp. 3096–3102, 1998.
[51] F. Sallusto, B. Palermo, D. Lenig, M. Miettinen, S. Matikainen, I. Julkunen, et al., “Distinct patterns and kinetics of chemokine production regulate dendritic cell function”, Eur. J. Immunol., vol. 29, pp. 1617–1625, 1999.
[52] Cella, F. Sallusto and A. Lanzavecchia, “Origin, maturation and antigen presenting function of dendritic cells”,Curr. Opin.Immunol., vol. 9, pp. 10–16, 1997.
[53] M .Cella , M. Salio, Y. Sakakibara, H. Langen, I. Julkunen and A. Lanzavecchia, “Maturation, activation, and protection of dendritic cells induced by double-stranded RNA”, J. Exp. Med.,vol. 189,pp. 821–829, 1999.
[54] Bertho, H. Adamski, L. Toujas, M. Debove, J. Davoust and V. Quillien, “Efficient migration of dendritic cells toward lymph node chemokines and induction of T(H)1 responses require maturation stimulus and apoptotic cell interaction”, Blood, vol. 106, pp. 1734–1741, 2005.
[55] O. Kim, H. J. Kim, K. Lee and H. S. Kim, “Generation of functionally mature dendritic cells from elutriated monocytes using polyinosinic : polycytidylic acid and soluble CD40 ligand for clinical application”, Clin. Exp. Immunol., vol. 154, pp. 365–374, 2008.
[56] M. Bonifaz, D. Bonnyay, K. Mahnke, M. Rivera, M. C. Nussenzweig, R. M. Steinman, “Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance”, J Exp Med., vol. 196, pp. 1627–1638, 2002.
[57] Hawiger, K. Inaba, Y. Dorsett, M. Guo, K. Mahnke, M. Rivera, et al., “Dendritic cells induce peripheral T cell unresponsive nessunder steady state conditions in vivo”, J. Exp. Med., vol. 194, pp. 769–779, 2001.
[58] V. Soares, G. A. Viani, S. L. Afonso, et al., “Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials”, BMC Cancer, vol. 8, pp. 7-153, 2007.
[59] R. M. Steinman, “Decisions About Dendritic Cells: Past, Present and Future”, Annu. Rev. Immunol., vol. 30,pp. 1–22, 2012.
[60] P. J. Tacken, C. G. Figdor, “Targeted antigen delivery and activation of dendritic cells in vivo: steps towards cost effective vaccines”, Semin Immunol., vol. 23, pp. 12–20, 2011.
[61] B. J. Flynn, K. Kastenmuller, U. Wille-Reece, G. D. Tomaras, M. Alam, R.W. Lindsay, A. M. Salazar, B. Perdiguero, C. E. Gomez, R. Wagner, et al., “Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates”, Proc. Natl. Acad. Sci. U SA., vol. 108, pp. 7131–7136, 2011.
[62] E. Klechevsky, A. L. Flamar, Y. Cao, J. P. Blanck, M. Liu, A. O`Bar, O. Agouna-Deciat, P. Klucar, L. Thompson-Snipes, S. Zurawski, et al., “Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR”, Blood., vol. 116, pp. 1685–1697, 2010.
[63] Meyer-Wentrup, A. Cambi, B. Joosten, M. W. Looman, I. J. de Vries, C. G. Figdor, G. J. Adema, “DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production”, J. Leukoc. Biol., vol. 85, pp. 518–525, 2009.
[64] O. Dakappagari, T. Maruyama, M. Renshaw, P. Tacken, C. Figdor, R. Torensma, M. A. Wild, D. Wu, K. Bowdish, A. Kretz-Rommel, “Internalizing antibodies to the C-type lectins, L-SIGN and DC-SIGN, inhibit viral glycoprotein binding and deliver antigen to human dendritic cells for the induction of T cell responses”, J Immunol., vol. 176, pp. 426–440, 2006.
[65] L. Ni, I. Gayet, S. Zurawski, D. Duluc, A. L. Flamar, X. H. Li, A. O`Bar, S. Clayton, A. K. Palucka, G. Zurawski, et al., “Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses”, J Immunol., vol.185, pp. 3504–3513, 2010.
[66] D. Sancho, D. Mourao-Sa, O. P. Joffre, O. Schulz, N. C. Rogers, D. J. Pennington, J. R. Carlyle, C. Reis e Sousa, “Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin”, J. Clin.Invest., vol. 118, pp. 2098–2110, 2008.
[67] V. Flacher, F. Sparber, C. H. Tripp, N. Romani, P. Stoitzner, “Targeting of epidermal Langerhans cells with antigenic proteins: attempts to harness their properties for immunotherapy”, Cancer Immunol Immunother., vol. 58, pp. 1137–1147, 2009.
[68] Caminschi, D. Vremec, F. Ahmet, M. H. Lahoud, J. A. Villadangos, K. M. Murphy, W. R. Heath, K. Shortman, “Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3(-/-) mice”, Mol. Immunol., vol. 50, pp. 9–17, 2012.
[69] O. P. Joffre, E. Segura, A. Savina, S. Amigorena, “Cross-presentation by dendritic cells”, Nat. Rev. Immunol. vol. 12, pp. 557–569, 2012.
[70] Y. Iwashita,K. Tahara, S. Goto, A. Sasaki, S. Kai, M. Seike, et al., “A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer”, Cancer Immunol. Immunother., vol. 52, pp. 155–161200, 2003.
[71] T. Nishiyama, M. Tachibana, Y. Horiguchi, K. Nakamura, Y. Ikeda, K. Takesako, et al., “Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide”, Clin. Cancer Res., vol. 7, pp. 23, 2001.
[72] A. Sharma, U. Koldovsky , S. Xu, R. Mick, R. Roses, E. Fitzpatrick,et al., “HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact DCIS”, Cancer, vol. 118, pp. 4354–4362, 2012.
[73] A. Amin, A. Z. Dudek, T. F. Logan, R. S. Lance, J. M. Holzbeierlein, J. J. Knox, et al., “Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): phase 2 study results”, J. Immunother”, Cancer, vol. 3, pp. 14, 2015.
[74] S. Polyzoidis and K. Ashkan,“DCVax(R)-L–developed by Northwest Biotherapeutics”, Hum. Vaccin. Immunother., vol. 10, pp. 3139–3145, 2014.
[75] P. L. Mitchell, M. A. Quinn, P. T. Grant, D. G. Allen, T. W. Jobling, S. C. White, et al., “A phase 2, single-arm study of an autologous dendritic cell treatment against mucin 1 in patients with advanced epithelial ovarian cancer”, J. Immunother. Cancer, vol. 2, pp. 16, 2014.
[76] H. J. Gray, B. Benigno, J. Berek, J. Chang, J. Mason, L. Mileshkin, et al., “Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial”, J. Immunother. Cancer, vol. 4, pp. 34, 2016.
[77] M. Kobayashi, A. Chiba, H. Izawa, E. Yanagida, M. Okamoto, S. Shimodaira, et al., “The feasibility and clinical effects of dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer.”, J. Ovarian Res., vol.7, pp. 48, 2014.
[78] L. Engell-Noerregaard, P. Kvistborg, M. B. Zocca, A. W. Pedersen, M. H. Claesson and A. Mellemgaard,“Clinical and immunological effects in patients with advanced non-small cell lung cancer after vaccination with dendritic cells exposed to an allogeneic tumor cell lysate”, World J. Vaccines, vol. 3, pp. 9, 2013.
[79] J. Small, P. F. Schellhammer, C. S. Higano, C. H. Redfern, J. J. Nemunaitis, F. H. Valone, et al., “Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer”, Clin. Oncol., vol. 24, pp. 3089–3094, 2006.
[80] R. So-Rosillo and E. J. Small, “Sipuleucel-T (APC8015) for prostate cancer”, Expert. Rev. Anticancer. Ther., vol.6, pp. 1163–1167, 2006.
[81] M. Podrazil, R. Horvath, E. Becht, D.Rozkova, P. Bilkova, K. Sochorova K, et al., “Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy inpatients with metastatic, castration-resistant prostate cancer”, Oncotarget, vol. 6, pp. 18192–18205, 2015.
[82] R. Dillman, S. Selvan, P. Schiltz, C. Peterson, K. Allen, C. Depriest, et al., “Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF:planned interim analysis”, Cancer Biother. Radiopharm., vol. 19, pp. 658–665, 2004.
[83] S. Mayanagi, M. Kitago, T. Sakurai, T. Matsuda, T. Fujita, H. Higuchi,et al., “Phase I pilot study of Wilms tumor gene 1 peptide pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer”, Cancer Sci., vol. 106, pp. 397–406, 2015.
[84] C. Toh, W. W. Wang, W. K. Chia, P. Kvistborg, L. Sun, K. Teo, et al., “Clinical benefit of allogeneic melanoma cell lysate-pulsed autologous dendritic cell vaccine in MAGE-positive colorectal cancer patients”, Clin. Cancer Res., vol. 15, pp. 7726–7736, 2009.
[85] P. P. Bapsy, B. Sharan, C. Kumar, R. P. Das, B. Rangarajan, M. Jain,et al. “Open-label,multi-center, non-randomized, single arm study to evaluate the safety and efficacy of dendritic cell immunotherapy in patients with refractory solid malignancies,on supportive care”, Cytotherapy, vol

Keywords
Dendritic Cells, Immunotherapy, Immunogenicity, T-cells..