Biological Efficacy of a Dendritic Cell-Based Vaccine in a Patient with Metastatic Colorectal Cancer
Keywords:Cancer immunotherapy, dendritic cells, metastatic colon cancer, vaccine, tumor lysate, immune response.
Colorectal cancer is a serious health problem affecting de novo more than one million people every year in the developed world. Despite recent advances in the development of novel therapeutic agents, metastatic colorectal cancer remains mostly incurable and its survival rates ominous even when patients respond to the most advanced treatments. Here, we describe a case in which a patient with metastatic colorectal cancer and high risk of relapse remains disease-free while being treated solely with twelve doses of autologous dendritic cells vaccines pulsed with autologous tumor lysate. A sustained, specific immune response elicited by vaccination has also been documented. Prior to receiving this experimental treatment, the patient had undergone both tumor resections and chemotherapy treatments six times, invariably relapsing/progressing within a year from each resection. We believe that the use of autologous vaccines consisting in dendritic cells pulsed with tumor lysate should be further investigate in human clinical trials, particularly in patients with minimal tumor burden and high risk of relapse. We also believe that this type of immunotherapy is more likely to be successful when used as an early rather than merely compassionate treatment option, given the fact that the more toxicity the immune system has received from previous approaches, the less it will be able to respond to tumor vaccination.
Terri A, Rick A, Priti B, et al. Cancer Facts & Figures 2012. Atlanta. Am Cancer Soc 2012.
Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst 2004; 96(15): 1128-32. http://dx.doi.org/10.1093/jnci/djh220
Allegra CJ, Yothers G, O'Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 2011; 29(1): 11-16. http://dx.doi.org/10.1200/JCO.2010.30.0855
Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009; 27(19): 3109-16. http://dx.doi.org/10.1200/JCO.2008.20.6771
Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124(7): 979-94.
Weiser MR, Landmann RG, Kattan MW, et al. Individualized prediction of colon cancer recurrence using a nomogram. J Clin Oncol 2008; 26(3): 380-85. http://dx.doi.org/10.1200/JCO.2007.14.1291
Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer 2006; 94(7): 982-99. http://dx.doi.org/10.1038/sj.bjc.6603033
Mayordomo JI, Zorina T, Storkus WJ, et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med 1995; 1(12): 1297-302. http://dx.doi.org/10.1038/nm1295-1297
Melief CJ. Cancer immunotherapy by dendritic cells. Immunity 2008; 29(3): 372-83. http://dx.doi.org/10.1016/j.immuni.2008.08.004
Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol 1999; 1(6): 362-68. http://dx.doi.org/10.1038/14058
Vulink A, Radford KJ, Melief C, Hart DN. Dendritic cells in cancer immunotherapy. Adv Cancer Res 2008; 99: 363-407. http://dx.doi.org/10.1016/S0065-230X(07)99006-5
Inoges S, Rodriguez-Calvillo M, Zabalegui N, et al. Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst 2006; 98(18): 1292-301. http://dx.doi.org/10.1093/jnci/djj358
Chaudhuri D, Suriano R, Mittelman A, Tiwari RK. Targeting the immune system in cancer. Curr Pharm Biotechnol 2009; 10(2): 166-84. http://dx.doi.org/10.2174/138920109787315114
Sobrero AF, Maurel J, Fehrenbacher L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26(14): 2311-319. http://dx.doi.org/10.1200/JCO.2007.13.1193
Onishi H, Morisaki T, Baba E, et al. Long-term vaccine therapy with autologous whole tumor cell-pulsed dendritic cells for a patient with recurrent rectal carcinoma. Anticancer Res 2011; 31(11): 3995-4005.