Vaccines in Non-Small Cell Lung Cancer

Luis Corrales-Rodriguez, Normand Blais, Denis Soulières

Centre Hospitalier de l’Université de Montréal, Hopital Notre-Dame, Montréal, Canada.
Hospital San Juan de Dios, San José, Costa Rica.

DOI: 10.4236/wjv.2013.31004                

Abstract

Immunotherapy as an option of treatment in cancer has experienced an important development with the inclusion of vaccines. In lung cancer this type of treatment has emerged and vaccines can be classified in three groups: antigen-specific vaccines, tumor cell vaccines, and dendritic cell vaccines. Emepepimut (L-BLP25) and MAGE-A3 have been the vaccines most widely studied. Their promising results with benefit in survival and limited toxicity in preclinical and clinical trials have led to phase III trials with results eagerly awaited. Other vaccines have been investigated, but results were not favorable or are still pending. Hopefully, vaccines could be an additional instrument for the treatment of lung cancer in the adjuvant or metastatic setting as time will unveil the results of current and future trials.

Keywords

Emepepimut-S; Immunotherapy; Lung Cancer; MAGE-A3; NSCLC; Review; Vaccine

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	[1] L. Corrales-Rodriguez, N. Blais and D. Soulieres, “Emepepimut-S for Non-Small Cell Lung Cancer,” Expert Opinion on Biological Therapy, Vol. 11, No. 8, 2011, pp. 1091-1097. doi:10.1517/14712598.2011.592490
[2]	F. Balkwill and A. Mantovani, “Inflammation and Cancer: Back to Virchow?” Lancet, Vol. 357, No. 9255, 2001, pp. 539-545. doi:10.1016/S0140-6736(00)04046-0
[3]	L. M. Coussens and Z. Werb, “Inflammation and Cancer,” Nature, Vol. 420, No. 6917, 2002, pp. 860-867. doi:10.1038/nature01322
[4]	P. A. Bradbury and F. A. Shepherd, “Immunotherapy for Lung Cancer,” Journal of Thoracic Oncology, Vol. 3, No. 6, 2008, pp. S164-S170. doi:10.1097/JTO.0b013e318174e9a7
[5]	J. Banchereau and R. M. Steinman, “Dendritic Cells and the Control of Immunity,” Nature, Vol. 392, No. 6673, 1998, pp. 245-252.
[6]	P. Bretscher and M. Cohn, “A theory of Self-Nonself Discrimination,” Science, Vol. 169, No. 3950, 1970, pp. 1042-1049. doi:10.1126/science.169.3950.1042
[7]	A. Ribas, L. H. Butterfield, J. A. Glaspy and J. S. Economou, “Current Developments in Cancer Vaccines and Cellular Immunotherapy,” Journal of Clinical Oncology, Vol. 21, No. 12, 2003, pp. 2415-2432.
[8]	J. Ferlay, H. R. Shin, F. Bray, D. Forman, C. Mathers and D. M. Parkin, “Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008,” International Journal of Cancer, Vol. 127, No. 12, 2010, pp. 2893-2917. doi:10.1002/ijc.25516
[9]	D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, “Global Cancer Statistics, 2002,” Oncology & Radiotherapy, Vol. 55, No. 2, 2005, pp. 74-108. doi:10.3322/canjclin.55.2.74
[10]	F. C. Detterbeck, D. J. Boffa and L. T. Tanoue, “The New Lung Cancer Staging System,” Chest, Vol. 136, No. 1, 2009, pp. 260-271. doi:10.1378/chest.08-0978
[11]	F. Bray, J. E. Tyczynski and D. M. Parkin, “Going Up or Coming Down? The Changing Phases of the Lung Cancer Epidemic from 1967 to 1999 in the 15 European Union Countries,” European Journal of Cancer, Vol. 40, No. 1, 2004, pp. 96-125. doi:10.1016/j.ejca.2003.08.005
[12]	P. J. Souquet, F. Chauvin, J. P. Boissel, R. Cellerino, Y. Cormier, P. A. Ganz, S. Kaasa, J. L. Pater, E. Quoix, E. Rapp, et al., “Polychemotherapy in Advanced Non Small Cell Lung Cancer: A Meta-Analysis,” Lancet, Vol. 342, No. 8862, 1993, pp. 19-21. doi:10.1016/0140-6736(93)91882-M
[13]	A. Jemal, M. J. Thun, L. A. Ries, H. L. Howe, H. K. Weir, M. M. Center, E. Ward, X. C. Wu, C. Eheman, R. Anderson, U. A. Ajani, B. Kohler and B. K. Edwards, “Annual Report to the Nation on the Status of Cancer, 1975-2005, Featuring Trends in Lung Cancer, Tobacco Use, and Tobacco Control,” Journal of the National Cancer Institute, Vol. 100, No. 23, 2008, pp. 1672-1694. doi:10.1093/jnci/djn389
[14]	S. Navaratnam, E. V. Kliewer, J. Butler, A. A. Demers, G. Musto and K. Badiani, “Population-Based Patterns and Cost of Management of Metastatic Non-Small Cell Lung Cancer after Completion of Chemotherapy Until Death,” Lung Cancer, Vol. 70, No. 1, 2010, pp. 110-115. doi:10.1016/j.lungcan.2010.01.012
[15]	Food and Drug Administration, “Approval Letter—Provenge,” Food and Drug Administration, Silver Spring, 2010.
[16]	P. W. Kantoff, C. S. Higano, N. D. Shore, E. R. Berger, E. J. Small, D. F. Penson, C. H. Redfern, A. C. Ferrari, R. Dreicer, R. B. Sims, Y. Xu, M. W. Frohlich and P. F. Schellhammer, “Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer,” The New England Journal of Medicine, Vol. 363, No. 5, 2010, pp. 411-422. doi:10.1056/NEJMoa1001294
[17]	C. Gridelli, A. Rossi, P. Maione, M. L. Ferrara, V. Castaldo and P. C. Sacco, “Vaccines for the Treatment of Non-Small Cell Lung Cancer: A Renewed Anticancer Strategy,” Oncologist, Vol. 14, No. 9, 2009, pp. 909-920. doi:10.1634/theoncologist.2009-0017
[18]	S. A. North, K. Graham, D. Bodnar and P. Venner, “A Pilot Study of the Liposomal MUC1 Vaccine BLP25 in Prostate Specific Antigen Failures after Radical Prostatectomy,” Journal of Urology, Vol. 176, No. 1, 2006, pp. 91-95. doi:10.1016/S0022-5347(06)00494-0
[19]	R. Sangha and S. North, “L-BLP25: A MUC1-Targeted Peptide Vaccine Therapy in Prostate Cancer,” Expert Opinion on Biological Therapy, Vol. 7, No. 11, 2007, pp. 1723-1730. doi:10.1517/14712598.7.11.1723
[20]	B. Agrawal, M. J. Krantz, M. A. Reddish and B. M. Longenecker, “Rapid Induction of Primary Human CD4+ and CD8+ T Cell Responses against Cancer-Associated MUC1 Peptide Epitopes,” International Immunology, Vol. 10, No. 12, 1998, pp. 1907-1916. doi:10.1093/intimm/10.12.1907
[21]	F. Ohyanagi, T. Horai, I. Sekine, N. Yamamoto, K. Nakagawa and M. Nishio, “L-BLP25 for Unresectable Stage III Non-Small Cell Lung Cancer after Primary Chemoradiotherapy in Japanese Patients: Preliminary Safety Results from a Phase I/II Study,” Journal of Clinical Oncology, Vol. 28, No. 15, 2010 , Article ID: e13153.
[22]	C. Butts, N. Murray, A. Maksymiuk, G. Goss, E. Marshall, D. Soulieres, Y. Cormier, P. Ellis, A. Price, R. Sawhney, M. Davis, J. Mansi, C. Smith, D. Vergidis, P. Ellis, M. MacNeil and M. Palmer, “Randomized Phase IIB Trial of BLP25 Liposome Vaccine in Stage IIIB and IV Non-Small-Cell Lung Cancer,” Journal of Clinical Oncology, Vol. 23, No. 27, 2005, pp. 6674-6681.
[23]	K. K. Bass and M. J. Mastrangelo, “Immunopotentiation with Low-Dose Cyclophosphamide in the Active Specific Immunotherapy of Cancer,” Cancer Immunology, Immunotherapy, Vol. 47, No. 1, 1998, pp. 1-12. doi:10.1007/s002620050498
[24]	G. D. MacLean, D. W. Miles, R. D. Rubens, M. A. Reddish and B. M. Longenecker, “Enhancing the Effect of THERATOPE Stn-KLH Cancer Vaccine in Patients with Metastatic Breast Cancer by Pretreatment with Low-Dose Intravenous Cyclophosphamide,” Journal of Immunotherapy with Emphasis on Tumor Immunology, Vol. 19, No. 4, 1996, pp. 309-316.
[25]	C. Butts, R. N. Murray, C. J. Smith, P. M. Ellis, K. Jasas, A. Maksymiuk, G. Goss, G. Ely, F. Beier and D. Soulieres, “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
[26]	ClinicalTrials.gov, “Cancer Vaccine Study for Stage III, Unresectable, Non-Small Cell Lung Cancer (NSCLC) in the Asian Population (INSPIRE),” The U.S. National Institutes of Health, Bethesda, 2011.
[27]	C. Butts, A. Maksymiuk, G. Goss, D. Soulieres, E. Marshall, Y. Cormier, P. Ellis, P. A. rice, R. Sawhney and N. Murray, “A Multi-Centre Phase IIB Randomized Controlled Study of BLP25 Liposome Vaccine (L-BLP25 or Stimuvax) for Active Specific Immunotherapy of Non-Small Cell Lung Cancer (NSCLC) Updated Survival Analysis,” Journal of Thoracic Oncology, Vol. 2, No. 8, 2007, pp. S332-S333.
[28]	C. Butts, H. Anderson, A. Maksymiuk, D. Vergidis, D. Soulières, Y. Cormier, M. Davis, E. Marshall, M. Falk and G. Goss, “Long-term Safety of BLP25 Liposome Vaccine (L-BLP25) in Patients (Pts) with Stage IIIB/IV Non-Small Cell Lung Cancer(NSCLC),” Journal of Clinical Oncology, Vol. 27, No. S15, 2009.
[29]	D. Soulieres, C. Smith, P. Ellis, N. Murray, K. Jasas, A. Maksymiuk, G. Goss, M. Falk and C. Butts, “A Multi-Centre, Open-Label Study to Assess the Safety of Stimuvax (BLP25 Liposome Vaccine or L-BLP25) in Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) with unresectable Stage III Disease,” Journal of Clinical Oncology, Vol. 25, No. S18, 2007, p. 3075.
[30]	http://www.emdserono.com/cmg.emdserono_us/en/images/StimuvaxPR%20-%20FDA%20lift%20NSCLC%20EMD%20SERONO%20VERSION%20FINAL_tcm115_54663.pdf
[31]	B. Gaugler, B. Van den Eynde, P. van der Bruggen, P. Romero, J. J. Gaforio, E. De Plaen, B. Lethe, F. Brasseur and T. Boon, “Human Gene MAGE-3 Codes for an Antigen Recognized on a Melanoma by Autologous Cytolytic T Lymphocytes,” The Journal of Experimental Medicine, Vol. 179, No. 3, 1994, pp. 921-930. doi:10.1084/jem.179.3.921
[32]	W. Sienel, C. Varwerk, A. Linder, D. Kaiser, M. Teschner, M. Delire, G. Stamatis and B. Passlick, “Melanoma Associated Antigen (MAGE)-A3 Expression in Stages I and II Non-Small Cell Lung Cancer: Results of a Multi-Center Study,” European Journal of Cardiothoracic Surgery, Vol. 25, No. 1, 2004, pp. 131-134. doi:10.1016/j.ejcts.2003.09.015
[33]	W. H. Kruit, H. H. van Ojik, V. G. Brichard, B. Escudier, T. Dorval, B. Dreno, P. Patel, N. van Baren, M. F. Avril, S. Piperno, A. Khammari, M. Stas, G. Ritter, B. Lethe, D. Godelaine, F. Brasseur, Y. Zhang, P. van der Bruggen, T. Boon, A. M. Eggermont and M. Marchand, “Phase 1/2 Study of Subcutaneous and Intradermal Immunization with a Recombinant MAGE-3 Protein in Patients with Detectable Metastatic Melanoma,” International Journal of Cancer, Vol. 117, No. 4, 2005, pp. 596-604. doi:10.1002/ijc.21264
[34]	J. Vansteenkiste, M. Zielinski, A. Linder, J. Dahabre, E. Esteban, W. Malinowski, J. Jassem, B. Passlick, F. Lehmann and V. Brichard, “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. S18, 2007, p. 7554.
[35]	J. Vansteenkiste, M. Zielinski, I. Dahabreh, A. Linder, F. Lehmann, O. Gruselle, P. Therasse, J. Louahed and V. Brichard, “Association of Gene Expression Signature and Clinical Efficacy of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) as Adjuvant Therapy in Resected Stage IB/II Non-Small Cell Lung Cancer (NSCLC),” Journal of Clinical Oncology, Vol. 26, No. S15, 2008.
[36]	http://clinicaltrials.gov/ct2/show/NCT00480025
[37]	C. Manegold, D. Gravenor, D. Woytowitz, et al., “Randomized Phase II Trial of a Toll-Like Receptor 9 Agonist Oligodeoxynucleotide, PF-3512676, in Combination with First-Line Taxane Plus Platinum Chemotherapy for Advanced-Stage Non-Small-Cell Lung Cancer,” Journal of Clinical Oncology, Vol. 26, No. 24, 2008, pp. 3979-3986.
[38]	H. Hemmi, O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, et al., “Toll-Like Receptor Recognizes Bacterial DNA,” Nature, Vol. 408, No. 6813, 2000, pp. 740-745. doi:10.1038/35047123
[39]	C. Manegold, N. van Zandwijk, et al., “A Phase III Randomized Study of Gemcitabine and Cisplatin with or without PF-3512676 (TLR9 Agonist) as First-Line Treatment of Advanced Non-Small-Cell Lung Cancer,” Annals of Oncology, Vol. 23, No. 1, 2012, pp. 72-77.
[40]	V. Hirsh, L. Paz-Ares, et al., “Randomized Phase III Trial of Paclitaxel/Carboplatin with or without PF-3512676 (Toll-Like Receptor 9 Agonist) as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer,” Journal of Clinical Oncology, Vol. 29, No. 19, 2011, pp. 2667-2674.
[41]	F. Kong, R. L. Jirtle, D. H. Huang, R. W. Clough and M. S. Anscher, “Plasma Transforming Growth Factor-Beta1 Level before Radiotherapy Correlates with Long Term Outcome of Patients with Lung Carcinoma,” Cancer, Vol. 86, No. 9, 1999, pp. 1712-1719. doi:10.1002/(SICI)1097-0142(19991101)86:9<1712::AID-CNCR12>3.0.CO;2-V
[42]	J. Nemunaitis, R. O. Dillman, 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,” Journal of Clinical Oncology, Vol. 24, No. 29, 2006, pp. 4721-4730.
[43]	http://clinicaltrials.gov/ct2/show/NCT00676507 “Phase III LucanixTM Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Frontline Chemotherapy (STOP)
[44]	B. Agrawal, M. J. Krantz, M. A. Reddish and B. M. Longenecker, “Cancer-Associated MUC1 Mucin Inhibits Human T-Cell Proliferation, Which Is Reversible by IL-2,” Nature Medicine, Vol. 4, No. 1, 1998, pp. 43-49. doi:10.1038/nm0198-043
[45]	E. Quoix, R. Ramlau, V. Westeel, Z. Papai, A. Madroszyk, et al., “Therapeutic Vaccination with TG4010 and First-Line Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Controlled Phase 2B Trial,” The Lancet Oncology, Vol. 12, No. 12, 2011, pp. 1125-1133. doi:10.1016/S1470-2045(11)70259-5
[46]	ClinicalTrials.gov, “Phase IIB/III of TG4010 Immunotherapy in Patients with Stage IV Non-Small Cell Lung Cancer (TIME),” 2012. http://clinicaltrials.gov/ct2/show/NCT01383148
[47]	G. J. Freeman, A. J. Long, Y. Iwai, K. Bourque, T. Chernova, et al., “Engagement of the PD-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation,” The Journal of Experimental Medicine, Vol. 192, No. 7, 2000, pp. 1027-1034.
[48]	S. L. Topalian, C. G. Drake and D. M. Pardoll, “Targeting the PD-1/B7-H1 (PD-L1) Pathway to Activate Anti-Tumor Immunity,” Current Opinion in Immunology, Vol. 24, No. 2, 2012, pp. 207-212.
[49]	S. L. Topalian, F. S. Hodi, J. R. Brahmer, S. N. Gettinger, et al., “Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer,” The New England Journal of Medicine, Vol. 366, No. 26, 2012, pp. 2443-2454.