Vacciner les cancers du sein réfractaires?
Dr Dominique-Jean Bouilliez (12/04/2011)
L'immunothérapie peptidique avec des peptides candidats individualisés a montré une certaine efficacité pour stimuler l'immunité anticancéreuse chez certains patients avec cancer avancé.
Une étude préliminaire effectuée chez 27 femmes avec cancer du sein réfractaire a montré que ce concept vaut la peine d'être étudié plus avant.
Dans cet essai clinique qui n'est pas encore terminé, les auteurs ont en effet constaté une réponse complète, 2 réponses partielles, 12 stabilisations et 6 progressions seulement. Mieux qu'encourageant dans ce contexte ?...
Toh U et coll. Immunologic and clinical effects of personalized selection of peptide vaccines in patients with refractory breast cancer. 12th St. Gallen International Breast Cancer Conference. 16-19 mars 2011. St. Gallen (Suisse).
Breast. 2007 Dec;16 Suppl 2:S20-6. Epub 2007 Aug 13.
Immunology and breast cancer: therapeutic cancer vaccines.
Department of Medicine, Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milano, Italy. email@example.com
Cancer immunosurveillance is a process that results from activity of recognition and destruction of cancer cells by innate and adaptive immune effector cells and molecules. Cancer cells can avoid immunosurveillance through the immunoselection, that is the development of poorly immunogenic tumor-cell variants, and through subversion of the immune system (also known as immunosubversion). Identification of tumor antigens (Ags) that can be recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. Breast cancer vaccines can induce immunogenic response against tumors weakly immunogenic; usually have a good tolerance and safety profile and can induce a long-term immune memory, critical to prevent efficiently tumor recurrence. Several studies evaluating breast cancer vaccines have been performed in patients with extended metastatic breast cancer, usually refractory to other standard treatments so that clinical efficacy was difficult to achieve. Significant immune responses against tumor Ags induced upon vaccinations were described to several tumor Ag vaccines. A better understanding of the relation between innate and adaptive immune responses, of the immune escape mechanisms employed by tumor cells and acknowledgment of the importance of both cell-mediated and humoral adaptive immunity for the control of tumor growth are necessary for leading to a more comprehensive immunotherapeutic approach in breast cancer.
PMID: 17706425 [PubMed - indexed for MEDLINE]
Jpn J Clin Oncol. 2006 Apr;36(4):231-6. Epub 2006 Apr 12.
A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: safety assessment based on the phase I data.
Morita S, Oka Y, Tsuboi A, Kawakami M, Maruno M, Izumoto S, Osaki T, Taguchi T, Ueda T, Myoui A, Nishida S, Shirakata T, Ohno S, Oji Y, Aozasa K, Hatazawa J, Udaka K, Yoshikawa H, Yoshimine T,Noguchi S, Kawase I, Nakatsuka S, Sugiyama H, Sakamoto J.
Department of Epidemiology and Health care Research, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. firstname.lastname@example.org
OBJECTIVE: We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies.
METHODS: Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment.
RESULTS: Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment.
CONCLUSION: This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.
PMID: 16611662 [PubMed - indexed for MEDLINE]