title: Immune response to postsurgical adjuvant active immunotherapy with Canvaxin polyvalent cancer vaccine: correlations with clinical course of patients with metastatic melanoma.
abstract: 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.
authors.affiliation: 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
authors.forename: D L
authors.initials: DL
authors.lastname: Morton
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines