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 — Oak Academic Publishing
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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
Department of Oncology, Herlev University Hospital, Herlev, Denmark
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DanDrit Biotech A/S, Copenhagen, Denmark
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DanDrit Biotech A/S, Copenhagen, Denmark
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DanDrit Biotech A/S, Copenhagen, Denmark
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Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
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Department of Oncology, Herlev University Hospital, Herlev, Denmark
1 Department of Oncology, Herlev University Hospital, Herlev, Denmark
2 DanDrit Biotech A/S, Copenhagen, Denmark
3 DanDrit Biotech A/S, Copenhagen, Denmark
4 DanDrit Biotech A/S, Copenhagen, Denmark
5 Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
6 Department of Oncology, Herlev University Hospital, Herlev, Denmark
Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac ? , Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN g EliSpot. Secondary objec tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten vaccinations. Seven patients remained in stable disease (SD) three months after the first vac cination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five patients showed an un expectedly prolonged survival. The treatment was well tolerated and only minor adverse events were reported. Quality of life did not change during the study period. In four of the seven patients with SD, vaccine-specific T cells were de tected by IFN γ EliSpot assays, whereas only one patient with progressive disease (PD) showed vaccine-specific re sponses. Conclusion: This DC-based vaccine trial has indicated a correlation between vaccine-specific immunity and sustained SD. Furthermore, we observed an unexpectedly prolonged survival in some patients, which may indicate delayed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac ? vaccine treatment in patients with progressive NSCLC.
A. Jemal, F. Bray, M. M. Center, J. Ferlay, et al., “Global Cancer Statistics,” Cancer Journal for Clinicians, Vol. 61, No. 2, 2011, pp. 69-90. doi:10.3322/caac.20107
J. Ferlay, D. M. Parkin and E. Steliarova-Foucher, “Estimates of Cancer Incidence and Mortality in Europe in 2008,” European Journal of Cancer, Vol. 46, No. 4, 2010, pp. 765-781. doi:10.1016/j.ejca.2009.12.014
L. S. Gloeckler Ries, M. E. Reichman, D. Riedel Lewis, et al., “Cancer Survival and Incidence from the Surveillance, Epidemiology, and End Results (SEER) Program,” The Oncologist, Vol. 8, No. 6, 2003, pp. 541-552. doi:10.1634/theoncologist.8-6-541
B. A. Quinn, N. Kasahara, F. Farzaneh, et al., “Recent Advances and Current Challenges in Tumor Immunology and Immunotherapy,” Molecular Therapy, Vol. 15, No. 6, 2007, pp. 1065-1071.
P. W. Kantoff, C. S. Higano, N. D. Shore, et al., “Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer,” The New England Journal of Medicine, Vol. 363, 2010, pp. 411-422. doi:10.1056/NEJMoa1001294
A. Pollack, “Approval for Drug That Treats Melanoma,” The New York Times, 25 March 2011.
C. Butts, R. N. Murray, C. J. Smith, et al., “A Multicenter Open-Label Study to Assess the Safety of a New Formulation of BLP25 Liposome Vaccine in Patients with Unresectable Stage III Non-Small-Cell Lung Cancer,” Clinical Lung Cancer, Vol. 11, No. 6, 2010, pp. 391-395. doi:10.3816/CLC.2010.n.101
J. Vansteenkiste, M. Zielinski, A. Linder, et al., “Final Results of a Multi-Center, Double-Blind, Randomized, Placebo-Controlled Phase II Study to Assess the Efficacy of MAGE-A3 Immunotherapeutic as Adjuvant Therapy in Stage IB/II Non-Small Cell Lung Cancer (NSCLC),” Journal of Clinical Oncology, Vol. 25, No. 18, 2007, p. 7554.
P. Tyagi and B. Mirakhur, “MAGRIT: The Largest-Ever Phase III Lung Cancer Trial Aims to Establish a Novel Tumor-Specific Approach to Therapy,” Clinical Lung Cancer, Vol. 10, No. 5, 2009, pp. 371-374. doi:10.3816/CLC.2009.n.052
B. T. Weinert, K. K. Krishnadath, F. Milano, et al., “Real-Time PCR Analysis of Genes Encoding Tumor Antigens in Esophageal Tumors and a Cancer Vaccine,” Cancer Immunity, Vol. 9, No. 1, 2009, p. 9.
M. J. Scanlan, A. J. Simpson and L. J. Old, “The Cancer/ Testis Genes: Review, Standardization, and Commentary,” Cancer Immunity, Vol. 4, No. 1, 2004, pp. 1-15.
W. Sienel, I. Mecklenburg, S. Dango, et al., “Detection of MAGE-A Transcripts in Bone Marrow Is an Independent Prognostic Factor in Operable Non-Small-Cell Lung Cancer,” Clinical Cancer Research, Vol. 13, No. 13, 2007, pp. 3840-3847. doi:10.1158/1078-0432.CCR-06-2507
S. Dango, X. T. Wang, M. Gold, et al., “Expression of Melanoma-Antigen-A (MAGE-A) in Disseminated Tumor Cells in Regional Lymph Nodes of Patients with Operable Non-Small Cell Lung Cancer,” Lung Cancer, Vol. 67, No. 3, 2010, pp. 290-295. doi:10.1016/j.lungcan.2009.04.012
M. Sugita, M. Geraci, B. Gao, et al., “Combined Use of Oligonucleotide and Tissue Microarrays Identifies Cancer/Testis Antigens as Biomarkers in Lung Carcinoma,” Cancer Research, Vol. 62, No. 14, 2002, pp. 3971-3979.
H. C. Toh, W. W. Wang, W. K. Chia, et al., “Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine inMAGE-Positive Colorectal Cancer Patients,” Clinical Cancer Research, Vol. 15, 2009, pp. 7726-7736. doi:10.1158/1078-0432.CCR-09-1537
P. Fayers, N. K. Aaronson, K. Bjordal, et al., “On Behalf of the EORTC Quality of Life Study Group. EORTC QLQ-C30 Scoring Manual (3rd Edition),” Brussels, EORTC Quality of Life Group 2001.
N. Romani, S. Gruner, D. Brang, et al., “Proliferating Dendritic Cell Progenitors in Human Blood,” The Journal of Experimental Medicine, Vol. 180, No. 1, 1994, pp. 83-93. doi:10.1084/jem.180.1.83
S. K. Burgdorf, A. Fischer, M. H. Claesson, et al., “Vaccination with Melanoma Lysate-Pulsed Dendritic Cells, of Patients with Advanced Colorectal Carcinoma: Report from a Phase I Study,” Journal of Experimental & Clinical Cancer Research, Vol. 25, No. 2, 2006, pp. 201-206.
P. Kvistborg, M. Boegh, A. W. Pedersen, et al., “Fast Generation of Dendritic Cells,” Cellular Immunology, Vol. 260, No. 1, 2009, pp. 56-62. doi:10.1016/j.cellimm.2009.09.003
J. W. Fay, A. K. Palucka, S. Paczesny, et al., “Long-Term Outcomes in Patients with Metastatic Melanoma Vaccinated with Melanoma Peptide-Pulsed CD34(+) Progenitor-Derived Dendritic Cells,” Cancer Immunology, Immunotherapy, Vol. 55, No. 10, 2006, pp. 1209-1218. doi:10.1007/s00262-005-0106-6
A. Hoos, G. Parmiani, K. Hege, et al., “Cancer Vaccine Clinical Trial Working Group. A Clinical Development Paradigm for Cancer Vaccines and Related Biologics,” Journal of Immunotherapy, Vol. 30, No. 1, 2007, pp. 1-15.
C. van der Lonchay, B. P. Connerotte, T. Hanagiri, et al., “Correlation between Tumor Regression and T Cell Responses in Melanoma Patients Vaccinated with a Mage Antigen,” Proceedings of the National Academy of Sciences, Vol. 101, No. 2, 2004, pp. 14631-1438. doi:10.1073/pnas.0405743101
N. Bercovici, N. Haicheur, S. Massicard, et al., “Analysis and Characterization of Antitumor T-Cell Response after Administration of Dendritic Cells Loaded with Allogeneic Tumor Lysate to Metastatic Melanoma Patients,” Journal of Immunotherapy, Vol. 31, No. 1, 2008, pp. 101-112. doi:10.1097/CJI.0b013e318159f5ba
I. de Vries, W. J. Lesterhuis, N. M. Scharenborg, et al., “Maturation of Dendritic Cells Is a Prerequisite for Inducing Immune Responses in Advanced Melanoma Patients,” Clinical Cancer Research, Vol. 9, No. 14, 2003, pp. 5091-5100.
I. de Vries, M. R. Bernsen, W. J. Lesterhuis, et al., “Immunomonitoring Tumor-Specific T Cells in Delayed-Type Hypersensitivity Skin Biopsies after Dendritic Cell Vaccination Correlates with Clinical Outcome,” Journal of Clinical Oncology, Vol. 23, No. 24, 2005, pp. 5779- 5787. doi:10.1200/JCO.2005.06.478
F. O. Nestle, S. Alijagic, M. Gilliet, et al., “Vaccination of Melanoma Patients with Peptide-or Tumor Lysate-Pulsed Dendritic Cells,” Nature Medicine, Vol. 4, No. 3, 1998, pp. 328-332. doi:10.1038/nm0398-328
J. D. Geiger, R. J. Hutchinson, L. F. Hohenkirk, et al., “Vaccination of Pediatric Solid Tumor Patients with Tumor Lysate-Pulsed Dendritic Cells Can Expand Specific T Cells and Mediate Tumor Regression,” Cancer Research, Vol. 61, No. 23, 2001, pp. 8513-8519.
M. S. Mitchell, W. Harel, R. A. Kempf, et al., “Active-Specific Immunotherapy for Melanoma,” Journal of Clinical Oncology, Vol. 8, No. 5, 1990, pp. 856-869.
M. Griffioen, M. Borghi, P. I. Schrier, et al., “Analysis of T-Cell Responses in Metastatic Melanoma Patients Vaccinated with Dendritic Cells Pulsed with Tumor Lysates,” Cancer Immunology, Immunotherapy, Vol. 53, No. 8, 2004, pp. 715-722. doi:10.1007/s00262-004-0514-z