Allogeneic tumor cell vaccines

Figures & data

Table 1. Overview of findings from allogeneic clinical trials for cancer immunotherapies

Cancer origin	Type of therapy	Phase	Total patients	Median overall survival	Reference
Breast	Allogeneic GM-CSF-secreting whole cell breast cancer vaccine	I	60	—	Emens, Armstrong 2004^108
Breast	Allogeneic costimulatory gene (CD80)-modified, HLA-A2-matched, breast cancer cell line	I	30	—	Dols, Smith et al. 2003^52
Breast	Allogeneic GM-CSF-secreting breast cancer cell lines (SKBR3 and T47D) alone or with CY and DOX	I	28	—	Emens, Asquith et al. 2009^109
Chronic myeloid leukemia	CML cell line modified to secrete GM-CSF administered with imatinib mesylate	I	19	—	Smith, Kasamon et al. 2010^61
Lung	Autologous DCs, generated by culturing CD14+ cells with GM-CSF and IL-4, were cultured with apoptotic bodies from 1650-TC expressing adenocarcinoma cell line, and then administered i.d.	I	14	—	Yannelli et al. 2005,^110 Hirschowitz et al. 2007^111
Lung	K562 cells genetically modified to secrete GM-CSF combined with autologous long tumor cells	I/II	86	5.4 mo	Nemunaitis, Jahan et al. 2006^112
Lung (NSCLC)	Administration of Belagenpumatucel-L (cocktail of 4 irradiated allogeneic NSCLC cell lines transfected with TGF-β2 antisense transgene)	II	75	14.5 mo	Nemunaitis et al. 2006^56
Lung (NSCLC)	Adminstration of irradiated whole cell (AD100) allogeneic vaccine transfected to express B7.1 along with either HLA-A1 or HLA-A2	I	19	18 mo	Raez, Cassileth et al. 2004^55
Lung (NSCLC)	Allogeneic tumor cells secreting endoplasmic reticulum-chaperone gp96-Ig-peptide complexes	I	19	16.5 mo	Raez, Walker et al. 2013^59
Melanoma	Administration of 3 irradiated allogeneic Cell lines with BCG	III	670	Discontinued No clinical benefit	—
Melanoma	Administration of Mel-D and Mel-S cell lysates (Melacine) with DETOX	I	17	—	Mitchell, Kanmitchell et al. 1988^64
Melanoma	Administration of Melacine with CY and IFN-α i.v. after 4 doses of Melacine	II, III	47	12.5 mo	Vaishampayan, Abrams et al. 2002^65
Melanoma	Melacine administration—investigate impact of class I antigen expression on relapse-free survival after adjuvant therapy with vaccine	III	689	5 y (relapse-free survival)	Sosman, Unger et al. 2002^66
Melanoma	Ex vivo loading of autologous DCs with antigens from apoptotic/necrotic allogeneic melanoma cells and subsequent adoptive transfer	I	16	—	Von Euw, Barrio et al. 2008^113
Melanoma	Administration of Cyp followed by VACCIMEL (mixture of 3 allogeneic cell lines)	II	30	—	Mordoh et al. 1997^114
Melanoma	Administration of VACCIMEL with rhGM-CSF	I	20	—	Barrio et al., 2006^115
Melanoma	Administration of autologous monocyte derived DCs loaded ex vivo with killed allogeneic Colo829 melanoma cells and activated with GM-CSF, IL-4, TNF-α and CD40 ligand	I	21	22.5 mo	Palucka, Ueno et al. 2006^69
Pancreatic cancer	Administration of allogeneic GM-CSF-secreting tumor vaccine eight weeks post pancreaticoduodenectomy	I	14	—	Jaffee et al. 2001^90
Prostate	Administration of 3 irradiated prostate cancer cell lines with BCG	IIb	44	—	—
Prostate	First administration of an allogeneic prostate cancer cell lines (PC3 and LNCap) modified to secrete GM-CSF (based on GVAX platform)	I/II	21	—	Simons, Carducci 2006^116
Prostate	Administration of an allogeneic prostate cancer cell lines (PC3 and LNCap) modified to secrete GM-CSF	I/II	34	34.9 mo (high dose); 24.0 mo (low dose)	Small, Sacks, Nemunaitis 2007^73
Prostate	Administration of GVAX plus Ipilimumab (fully human IgG CTLA-4 blocking Ab)	I	12	29.2 mo	Van den Eertwegh, Versluis, van den Berg 2012^117
Prostate	Administration of 2 allogeneic prostate-carcinoma cell lines that are genetically engineered to secrete GM-CSF	I/II	80	35.0 mo (high-dose); 20.0 mo (mid-dose), 23.1 mo (low-dose)	Higano, Corman, Smith et al. 2008^77
Prostate	Administration of LNCaP modified using retroviral vector to secrete IL-2 and IFN-γ	I	6	—	Brill, Kuebler, Pohla et al. 2007^118
Prostate	Administration of LNCaP modified using retroviral vector to secrete IL-2 and IFN-γ	I/II	30	32 mo	Brill, Kuebler, Pohla, Buchner 2009^119
Prostate	Administration of whole cell vaccine consisting of a mixture of 3 prostate cancer cell lines along with Mycobacterium vaccae (SRL172)	I/II	60	—	Eaton, Perry et al. 2002^71
Colon	Administration of 3 melanoma cell lines with BCG	I	27	12.9 mo	Habal, Gupta et al. 2001^93
Renal	Administration of two renal cancer cell lines genetically modified to express IL-7 and B7-1	I	10	40 mo	Westermen et al. 2011^94

A summary of clinical trials for allogeneic cancer immunotherapies lists the type of cancer, type of therapy, clinical trial phase, patients enlisted, median survival (if listed), and reference.

Table 2. Known TAAs of various cancers

Cancer origin	TAAs
Breast cancer	MUC 1, MUC 4,^99 Tn, T,^100 STn,^101 Her2/Neu,^102 BAGE, CAMEL, MAGE A1, Mammaglobin-A, TRAG-3, ML-IAP, Survivin, WT-1^103
Leukemia	hTERT, WT1, PRTN3, BCL2, LAMR1, PRAME, RHAMM/HMMR, G250/CA9^104
Lung cancer	MAGE-A3/4, NY-ESO-1, MAGE-A10, SOX2, CAGE, GBU4–5, Cyclin A, Cyclin B1, c-myc, STEAP, p53, Annexin 1, IMP1, p62/IMP2, CDK2, Survivin^103
Melanoma	MART, gp100, Tyrosinase, EBV BMLF1, CMV pp65,^105 BAGE, MAGE-A1/2/3/4/6/10/12, CAMEL, SSX2, TRAG-3, Melan-A, TRP1/2^103
Prostate cancer	PSA, PSMA, Eph2A, FGF-5, hTERT, AFP, GAGE-1/2/8, MAGE-A1, CAMEL, TRAG-3^103
Ovarian cancer	DAM 6–10, HER2/neu, hTERT, AIM-2^a, Cyp-B, ART-4, G250, Adipophilin^103
Pancreatic cancer	MUC 1, KRAS, EGFR,^84 Mesothelin,^106 p53^107

List of selected TAAs for breast cancer, leukemia, lung cancer, melanoma, prostate cancer, ovarian cancer, and pancreatic cancer.

Emens LA, Armstrong D, Biedrzycki B, Davidson N, Davis-Sproul J, Fetting J, Jaffee E, Onners B, Piantadosi S, Reilly RT, et al. A phase I vaccine safety and chemotherapy dose-finding trial of an allogeneic GM-CSF-secreting breast cancer vaccine given in a specifically timed sequence with immunomodulatory doses of cyclophosphamide and doxorubicin. Hum Gene Ther 2004; 15:313 - 37; http://dx.doi.org/10.1089/104303404322886165; PMID: 15018740

 PubMed Web of Science ®Google Scholar

Dols A, Smith JW 2nd, Meijer SL, Fox BA, Hu HM, Walker E, Rosenheim S, Moudgil T, Doran T, Wood W, et al. Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: clinical and immunological results. Hum Gene Ther 2003; 14:1117 - 23; http://dx.doi.org/10.1089/104303403322124828; PMID: 12885350

 PubMed Web of Science ®Google Scholar

Emens LA, Asquith JM, Leatherman JM, Kobrin BJ, Petrik S, Laiko M, Levi J, Daphtary MM, Biedrzycki B, Wolff AC, et al. Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol 2009; 27:5911 - 8; http://dx.doi.org/10.1200/JCO.2009.23.3494; PMID: 19805669

 PubMed Web of Science ®Google Scholar

Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, Garrett-Mayer E, Tsai HL, Qin L, Chia C, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res 2010; 16:338 - 47; http://dx.doi.org/10.1158/1078-0432.CCR-09-2046; PMID: 20048335

 PubMed Web of Science ®Google Scholar

Yannelli JR, Sturgill J, Foody T, Hirschowitz E. The large scale generation of dendritic cells for the immunization of patients with non-small cell lung cancer (NSCLC). Lung Cancer 2005; 47:337 - 50; http://dx.doi.org/10.1016/j.lungcan.2004.08.008; PMID: 15713517

 PubMed Web of Science ®Google Scholar

Hirschowitz EA, Foody T, Hidalgo GE, Yannelli JR. Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells. Lung Cancer 2007; 57:365 - 72; http://dx.doi.org/10.1016/j.lungcan.2007.04.002; PMID: 17509725

 PubMed Web of Science ®Google Scholar

Nemunaitis J, Jahan T, Ross H, Sterman D, Richards D, Fox B, Jablons D, Aimi J, Lin A, Hege K. Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer. Cancer Gene Ther 2006; 13:555 - 62; http://dx.doi.org/10.1038/sj.cgt.7700922; PMID: 16410826

 PubMed Web of Science ®Google Scholar

Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J, Tong A, Kumar P, Pappen B, Hamilton C, et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol 2006; 24:4721 - 30; http://dx.doi.org/10.1200/JCO.2005.05.5335; PMID: 16966690

 PubMed Web of Science ®Google Scholar

Raez LE, Cassileth PA, Schlesselman JJ, Sridhar K, Padmanabhan S, Fisher EZ, Baldie PA, Podack ER. Allogeneic vaccination with a B7.1 HLA-A gene-modified adenocarcinoma cell line in patients with advanced non-small-cell lung cancer. J Clin Oncol 2004; 22:2800 - 7; http://dx.doi.org/10.1200/JCO.2004.10.197; PMID: 15254047

 PubMed Web of Science ®Google Scholar

Raez L, Walker G, Baldie P, Fisher E, Gomez J, Tolba K, Santos E, Podack E. CD8 T cell response in a phase I study of therapeutic vaccination of advanced NSCLC with allogeneic tumor cells secreting endoplasmic reticulum-chaperone gp96-Ig-peptide complexes. Advances in Lung Cancer 2013; 2:9 - 18; http://dx.doi.org/10.4236/alc.2013.21002

 Google Scholar

Mitchell MS, Kan-Mitchell J, Kempf RA, Harel W, Shau HY, Lind S. Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant. Cancer Res 1988; 48:5883 - 93; PMID: 3262416

 PubMed Web of Science ®Google Scholar

Vaishampayan U, Abrams J, Darrah D, Jones V, Mitchell MS. Active immunotherapy of metastatic melanoma with allogeneic melanoma lysates and interferon alpha. Clin Cancer Res 2002; 8:3696 - 701; PMID: 12473578

 PubMed Web of Science ®Google Scholar

Sosman JA, Unger JM, Liu PY, Flaherty LE, Park MS, Kempf RA, Thompson JA, Terasaki PI, Sondak VK, Southwest Oncology Group. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. J Clin Oncol 2002; 20:2067 - 75; http://dx.doi.org/10.1200/JCO.2002.08.072; PMID: 11956267

 PubMed Web of Science ®Google Scholar

von Euw EM, Barrio MM, Furman D, Levy EM, Bianchini M, Peguillet I, Lantz O, Vellice A, Kohan A, Chacón M, et al. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression. J Transl Med 2008; 6:6; http://dx.doi.org/10.1186/1479-5876-6-6; PMID: 18221542

 PubMed Web of Science ®Google Scholar

Mordoh J, Kairiyama C, Bover L, Solarolo E. Allogeneic cells vaccine increases disease-free survival in stage III melanoma patients. A non randomized phase II study. Medicina (B Aires) 1997; 57:421 - 7; PMID: 9674264

 PubMed Web of Science ®Google Scholar

Barrio MM, de Motta PT, Kaplan J, von Euw EM, Bravo AI, Chacón RD, Mordoh J. A phase I study of an allogeneic cell vaccine (VACCIMEL) with GM-CSF in melanoma patients. J Immunother 2006; 29:444 - 54; http://dx.doi.org/10.1097/01.cji.0000208258.79005.5f; PMID: 16799340

 PubMed Web of Science ®Google Scholar

Palucka AK, Ueno H, Connolly J, Kerneis-Norvell F, Blanck J-P, Johnston DA, Fay J, Banchereau J. Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. J Immunother 2006; 29:545 - 57; http://dx.doi.org/10.1097/01.cji.0000211309.90621.8b; PMID: 16971810

 PubMed Web of Science ®Google Scholar

Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower RC, et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001; 19:145 - 56; PMID: 11134207

 PubMed Web of Science ®Google Scholar

Simons JW, Carducci MA, Mikhak B, Lim M, Biedrzycki B, Borellini F, Clift SM, Hege KM, Ando DG, Piantadosi S, et al. Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer. Clin Cancer Res 2006; 12:3394 - 401; http://dx.doi.org/10.1158/1078-0432.CCR-06-0145; PMID: 16740763

 PubMed Web of Science ®Google Scholar

Small EJ, Sacks N, Nemunaitis J, Urba WJ, Dula E, Centeno AS, Nelson WG, Ando D, Howard C, Borellini F, et al. Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin Cancer Res 2007; 13:3883 - 91; http://dx.doi.org/10.1158/1078-0432.CCR-06-2937; PMID: 17606721

 PubMed Web of Science ®Google Scholar

van den Eertwegh AJM, Versluis J, van den Berg HP, Santegoets SJAM, van Moorselaar RJA, van der Sluis TM, Gall HE, Harding TC, Jooss K, Lowy I, et al. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol 2012; 13:509 - 17; http://dx.doi.org/10.1016/S1470-2045(12)70007-4; PMID: 22326922

 PubMed Web of Science ®Google Scholar

Higano CS, Corman JM, Smith DC, Centeno AS, Steidle CP, Gittleman M, Simons JW, Sacks N, Aimi J, Small EJ. Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer 2008; 113:975 - 84; http://dx.doi.org/10.1002/cncr.23669; PMID: 18646045

 PubMed Web of Science ®Google Scholar

Brill TH, Kübler HR, von Randenborgh H, Fend F, Pohla H, Breul J, Hartung R, Paul R, Schendel DJ, Gansbacher B. Allogeneic retrovirally transduced, IL-2- and IFN-gamma-secreting cancer cell vaccine in patients with hormone refractory prostate cancer--a phase I clinical trial. J Gene Med 2007; 9:547 - 60; http://dx.doi.org/10.1002/jgm.1051; PMID: 17514769

 PubMed Web of Science ®Google Scholar

Brill TH, Kübler HR, Pohla H, Buchner A, Fend F, Schuster T, van Randenborgh H, Paul R, Kummer T, Plank C, et al. Therapeutic vaccination with an interleukin-2-interferon-gamma-secreting allogeneic tumor vaccine in patients with progressive castration-resistant prostate cancer: a phase I/II trial. Hum Gene Ther 2009; 20:1641 - 51; http://dx.doi.org/10.1089/hum.2009.101; PMID: 19671000

 PubMed Web of Science ®Google Scholar

Eaton JD, Perry MJA, Nicholson S, Guckian M, Russell N, Whelan M, Kirby RS. Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer. BJU Int 2002; 89:19 - 26; http://dx.doi.org/10.1046/j.1464-410X.2002.02572.x; PMID: 11849155

 PubMed Web of Science ®Google Scholar

Habal N, Gupta RK, Bilchik AJ, Yee R, Leopoldo Z, Ye W, Elashoff RM, Morton DL. CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer. Ann Surg Oncol 2001; 8:389 - 401; http://dx.doi.org/10.1007/s10434-001-0389-6; PMID: 11407512

 PubMed Web of Science ®Google Scholar

Westermann J, Flörcken A, Willimsky G, van Lessen A, Kopp J, Takvorian A, Jöhrens K, Lukowsky A, Schönemann C, Sawitzki B, et al. Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study. Gene Ther 2011; 18:354 - 63; http://dx.doi.org/10.1038/gt.2010.143; PMID: 21068778

 PubMed Web of Science ®Google Scholar

Rakha EA, Boyce RWG, Abd El-Rehim D, Kurien T, Green AR, Paish EC, Robertson JF, Ellis IO. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 2005; 18:1295 - 304; http://dx.doi.org/10.1038/modpathol.3800445; PMID: 15976813

 PubMed Web of Science ®Google Scholar

Springer GF. Immunoreactive T and Tn epitopes in cancer diagnosis, prognosis, and immunotherapy. J Mol Med (Berl) 1997; 75:594 - 602; http://dx.doi.org/10.1007/s001090050144; PMID: 9297627

 PubMed Web of Science ®Google Scholar

Brockhausen I. Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep 2006; 7:599 - 604; http://dx.doi.org/10.1038/sj.embor.7400705; PMID: 16741504

 PubMed Web of Science ®Google Scholar

Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124:966 - 78; PMID: 10888772

 PubMed Web of Science ®Google Scholar

Novellino L, Castelli C, Parmiani G. A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 2005; 54:187 - 207; http://dx.doi.org/10.1007/s00262-004-0560-6; PMID: 15309328

 PubMed Web of Science ®Google Scholar

Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, Dohner K, Schlenk RF, Pollack JR, Dohner H, et al. Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches. Blood 2006; 108:4109 - 17; http://dx.doi.org/10.1182/blood-2006-01-023127; PMID: 16931630

 PubMed Web of Science ®Google Scholar

Lee PP, Yee C, Savage PA, Fong L, Brockstedt D, Weber JS, Johnson D, Swetter S, Thompson J, Greenberg PD, et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 1999; 5:677 - 85; http://dx.doi.org/10.1038/9525; PMID: 10371507

 PubMed Web of Science ®Google Scholar

Laheru D, Biedrzycki B, Thomas AM, Jaffee EM. Development of a cytokine-modified allogeneic whole cell pancreatic cancer vaccine. In: Su GH, ed. Methods in Molecular Medicine, 2005:299-327.

 Google Scholar

Hassan R, Ho M. Mesothelin targeted cancer immunotherapy. Eur J Cancer 2008; 44:46 - 53; http://dx.doi.org/10.1016/j.ejca.2007.08.028; PMID: 17945478

 PubMed Web of Science ®Google Scholar

Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut 2007; 56:1134 - 52; PMID: 17625148

 PubMed Web of Science ®Google Scholar