Abstract
Cancer is lethal because of metastatic spread, and is seldom curable, even in patients who can be rendered free of disease. Autologous, proliferating, self-renewing tumor cells (cancer stem cells and/or early progenitor cells), which are responsible for metastatic tumors, could be excellent sources of antigen for vaccines that could be used for the active specific immunotherapy of patients with advanced cancer. We have established proliferating pure tumor cell cultures from cancer samples, followed by further expansion for patient-specific therapeutic purposes. In clinical trials, patients were treated with a series of s.c. injections of irradiated autologous tumor cells (TCV), or autologous dendritic cells (DCV), loaded with antigens from their tumor cell line. Cell lines were successfully established for nearly half of patients, with the highest success rates in melanoma, renal cell, sarcoma, and glioblastoma. For patients with melanoma and renal cell, who were treated with TCV, observed 5-year survival rates were nearly three times longer than national figures. For patients with melanoma who were treated with DCV, the 5-year survival rate was five times greater than national estimates. In a randomized trial comparing DCV and TCV in patients with metastatic melanoma, at a median follow up of 2 years, survival is better in patients treated with DCV. Patient-specific active immunotherapy with antigens from autologous proliferating, self-renewing tumor cells is a feasible approach. Such treatment is associated with encouraging long-term survival rates, and results are superior in patients treated with DCV loaded with antigen from such cells. A higher success rate of establishing cancer stem cell cultures is needed, and additional clinical trials will be required to establish the clinical benefit.
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References
Cornforth AN, Lee GJ, Fowler AW, Carbonell DJ, Dillman RO (2009) Increases in serum TARC/CCL17 levels are associated with progression-free survival in advanced melanoma patients in response to dendritic cell-based immunotherapy. Clin Immunol 29:657–664
Cornforth AN, Fowler AW, Carbonell DJ, Dillman RO (2011a) Resistance to the proapoptotic effects of interferon-gamma on melanoma cells used in patient-specific dendritic cell immunotherapy is associated with improved overall survival. Cancer Immunol Immunother 60:123–131
Cornforth AN, Fowler AW, Carbonell DJ, Fan E, Dillman RO (2011b) Characterization of interferon-γ-treated melanoma tumor cells for use in dendritic cell-based immunotherapy. Cancer Biother Radiopharm 26:345–351
Cornforth AN, Lee G, Dillman RO (2011c) Autologous peripheral blood mononuclear cell recognition of autologous proliferating tumor cells in the context of a patient-specific vaccine trial. J Biomed Biotechnol 2011:635850
Dillman RO (2009) Antibody therapy. In: Oldham RK, Dillman RO (eds) Principles of cancer biotherapy, vol 5th. Springer, Dordrecht, pp 303–406
Dillman RO (2011) Cancer immunotherapy. Cancer Biother Radiopharm 26:1–64
Dillman RO, Nayak SK, Beutel L (1993) Establishing in vitro cultures of autologous tumor cells for use in active specific immunotherapy. J Immunother 14:65–69
Dillman RO, Nayak SK, Brown JV, Mahdavi K, Beutel LD (1999) The feasibility of using short-term cultures of ovarian cancer cells for use as autologous tumor cell vaccines as adjuvant treatment of advanced ovarian cancer. Cancer Biother Radiopharm 14:443–449
Dillman RO, Beutel LD, Barth NM, de Leon C, O’Connor AA, DePriest C, Nayak SK (2002) Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival. Cancer Biother Radiopharm 17:51–66
Dillman RO, Wiemann M, Nayak SK, de Leon C, Hood K, DePriest C (2003) Interferon-gamma or granulocyte macrophage colony stimulating factor administered as adjuvants with a vaccine of irradiated autologous tumor cells from short-term cell line cultures: a randomized phase II trial of the Cancer Biotherapy Research Group. J Immunother 26:367–373
Dillman RO, Barth NM, Selvan SR, Beutel LD, DePriest C, de Leon C, Peterson C, Nayak S (2004a) Phase I/II trial of autologous tumor cell line-derived vaccine for recurrent or metastatic sarcomas. Cancer Biother Radiopharm 19:581–588
Dillman RO, Barth NM, VanderMolen LA, Mahdavi K, Beutel LD, de Leon C, DePriest C, Nayak S (2004b) Autologous tumor cell line-derived vaccine for patient-specific treatment of advanced renal cell carcinoma. Cancer Biother Radiopharm 19:570–580
Dillman RO, Beutel LD, DePriest C, Schiltz PM, Selvan SR, Nayak SK (2005) Cancer vaccine potency: is there a dose/response relationship for patient-specific vaccines and clinical outcomes? Cancer Biother Radiopharm 20:373–378
Dillman RO, Selvan SR, Schiltz PM (2006) Patient-specific dendritic cell vaccines for metastatic melanoma. N Engl J Med 355:1179–1181
Dillman RO, DePriest C, de Leon C, Barth NM, Schwartzberg LS, Beutel LD, Schiltz PM, Nayak SK (2007) Patient-specific vaccines derived from autologous tumor cell lines as active specific immunotherapy: results of exploratory phase I/II trials in patients with metastatic melanoma. Cancer Biother Radiopharm 22:309–321
Dillman RO, Selvan SR, Schiltz PM, McClay EF, Barth NM, DePriest C, de Leon C, Mayorga C, Cornforth AN, Allen K (2009) Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific anti-tumor vaccines in patients with metastatic melanoma: final report. Cancer Biother Radiopharm 24:311–319
Dillman RO, Nanci AA, Williams ST, Kim RB, Hafer RL, Coleman CL, Wang PC, Duma CM, Chen PV, Selvan SR, Cornforth AN, Depriest C (2010) Durable complete response of refractory, progressing metastatic melanoma after treatment with a patient-specific vaccine. Cancer Biother Radiopharm 25:553–557
Dillman RO, Fogel GB, Cornforth AN, DePriest C (2011) Features associated with survival in metastatic melanoma patients treated with patient-specific vaccines consisting of proliferating autologous tumor cells and autologous dendritic cells. Cancer Biother Radiopharm 26:407–415
Dillman RO, Cornforth AN, DePriest C, McClay EF, Amatruda TT, Carbonell D, de Leon C, Mayorga C, Ellis R, Cubellis J (2012) Randomized trial of autologous dendritic cell vs tumor cell vaccines in patients with metastatic melanoma. Proc Am Assoc Cancer Res (Abstr. 3703)
Hersey P, Coates AS, McCarthy WH, Thompson JF, Sillar RW, McLeod R, Gill PG, Coventry BJ, McMullen A, Dillon H, Simes RJ (2002) Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial. J Clin Oncol 20:4181–4190
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723
Hoover JC Jr, Brandhorst JS, Peters LC, Surdyke MG, Takesheta Y, Madariaga J, Muenz LR, Hanna MG Jr (1993) Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial. J Clin Oncol 11:390–399
Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PR, IMPACT Study Investigators (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422
Kirkwood JM, Ibrahim JG, Sosman JA, Sondak VK, Agarwala SS, Ernstoff MS, Rao U (2001) High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol 19:2370–2380
Lawson DH, Lee SJ, Tarhini AA, Margolin MS, Ernstoff MS, Kirkwood JM (2010) E4697: phase III cooperative group study of yeast-derived granulocyte macrophage colony-stimulating factor (GM-CSF) versus placebo as adjuvant treatment of patients with completely resected stage II-IV melanoma. J Clin Oncol 28:15s (suppl; abstr 8504)
Mitchell MS, Abrams J, Thompson JA, Kashani-Sabet M, DeConti RC, Hwu WJ, Atkins MB, Whitman E, Ernstoff MS, Haluska FG, Jakowatz JG, Das Gupta TK, Richards JM, Samlowski WE, Costanzi JJ, Aronson FR, Deisseroth AB, Dudek AZ, Jones VE (2007) Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for resected stage III cutaneous melanoma. J Clin Oncol 25:2078–2085
Morton DL, Mozzillo N, Thompson JF, Kelley MC, Faiies M, Wagner J, Schneebaum S, Schuchter L, Gammon G, Leahsoof R, MMAIT Clinical Trials Group (2007) An international, randomized, phase III trial of bacillus calmette-guerin (BCG) plus allogeneic melanoma vaccine (MCV) or placebo after complete resection of melanoma metastatic to regional or distant sites. J Clin Oncol 25:474s (abstr 8508)
Nayak SK, Dillman RO (1991) Establishment of multiple tumor cell lines from a patient with melanoma: a simple method to control fibroblast growth. Clin Biotechnol 3:237–242
Schiltz PM, Dillman RO, Korse CM, Cubellis JM, Lee GJ, De Gast GC (2008) Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells. Cancer Biother Radiopharm 23:214–221
Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P (2011) Gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 364:2119–2127
Selvan SR, Dillman RO, Fowler AW, Carbonell DJ, Ravindranath MH (2008) Monitoring response to treatment in melanoma patients: potential of a serum glycomic marker. Int J Cancer 122:1374–1383
Selvan SR, Carbonell DJ, Fowler AW, Beatty AR, Ravindranath MH, Dillman RO (2010) Establishment of stable cell lines for personalized melanoma cell vaccine. Melanoma Res 20:280–292
Sondak VK, Liu PY, Tuthill RJ, Kempf RA, Unger JM, Sosman JA, Thompson JA, Weiss GR, Redman BG, Jakowatz JG, Noyes RD, Flaherty LE (2002) Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the southwest oncology group. J Clin Oncol 20:2058–2066
Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A, Yuh L, Gupta R, Srivastava PK, C-100-21 Study Group (2008) 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 26:955–962
Wallack MK, Sivanandham M, Balch CM, Urist MM, Bland KI, Murray D, Robinson WA, Flaherty L, Richards JM, Bartolucci AA, Rosen L (1998) Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. J Am Coll Surg 187:69–77
Warren TL, Weiner GJ (2000) Uses of granulocyte-macrophage colony- stimulating factor in vaccine development. Curr Opin Hematol 7:168–173
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Dillman, R.O., Cornforth, A.N., DePriest, C. (2013). Cancer Stem Cell Antigens from Autologous Tumor Cell Lines in Patient-Specific Active Immunotherapy for Metastatic Cancer. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 9. Stem Cells and Cancer Stem Cells, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5645-8_26
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