Immune response to postsurgical adjuvant active immunotherapy with Canvaxin polyvalent cancer vaccine: correlations with clinical course of patients with metastatic melanoma.
The efficacy of cytoreductive surgery for metastatic melanoma depends in part on the patient's immune response, which can be modulated by post-operative active immunotherapy with Canvaxin therapeutic polyvalent cancer vaccine (CancerVax Corp., Carlsbad, CA). Canvaxin vaccine induces polyvalent humoral and cell-mediated immune responses to a wide variety of protein and ganglioside melanoma antigens; these responses correlate with subsequent prognosis in immunized patients. Matched-pair analyses of data from extensive phase II trials have demonstrated a consistent overall survival (OS) benefit for Canvaxin therapy in stage IV melanoma (five-year OS of 39% for 107 vaccine patients versus 20% for 107 non-vaccine patients; P = .0009) and stage III melanoma (five-year OS of 49% for 739 vaccine patients versus 37% for 739 non-vaccine patients; P = .0001). Vaccine-induced immune responses have been correlated with survival after resection of local, regional, and distant melanoma. In 77 patients who received Canvaxin vaccine after resection of stage IV melanoma, five-year OS rate was 75% for patients with an elevated level of IgM antibodies against a 90-kD glycoprotein antigen (TA90) expressed by the vaccine, and a strong delayed-type hypersensitivity (DTH) response to the vaccine; by contrast, survival was 36% for patients who had either an elevated IgM response or a strong DTH response, and only 8% if neither response was strong (P < .001). In 59 patients with resected stage III melanoma, both cellular (DTH) and humoral (anti-TA90 IgG and IgM antibodies) immune responses impacted survival (P = 0.046, 0.0005, and 0.0053, respectively). In stage II melanoma, five-year OS and disease-free survival rates were 94% and 89%, respectively, when maximal anti-TA90 IgM titre was at least 1:800, compared to only 52% and 17%, respectively, for lower titres (P = .0001). Cumulatively, these data represent the largest phase II experience for any cancer vaccine and indicate the clinical efficacy of stimulating a patient's endogenous immune response to melanoma.
Morton
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The Sonya Valley Ghidossi Vaccine Laboratory, Roy E. Coats Research Laboratories, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, CA 90404, USA. mortond@jwci.org
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D016233:Immunotherapy, Active; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D009362:Neoplasm Metastasis; D011182:Postoperative Care
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines