M-Vax: an autologous, hapten-modified vaccine for human cancer.
The author has devised a novel approach to the immunotherapy of cancer based on modification of autologous tumor cells with the hapten, dinitrophenyl (DNP). This technology is being developed by AVAX Technologies (MO, USA) as a treatment for melanoma under the brand name, M-Vax. The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with bacille Calmette-Guerin as an immunological adjuvant. Administration of DNP vaccine to patients with metastatic melanoma induces a unique reaction--the development of inflammation in metastatic masses. Following DNP-vaccine treatment, almost all patients develop delayed-type hypersensitivity (DTH) to autologous, DNP-modified melanoma cells and about half also exhibit DTH to autologous, unmodified tumor cells. The toxicity of the vaccine is mild, consisting mainly of papules or pustules at the injection sites. Clinical trials have been conducted in two populations of melanoma patients: Stage IV with measurable metastases, and clinical Stage III patients rendered tumor-free by lymphadenectomy. There were 11 antitumor responses in 83 patients with measurable metastases: two complete, four partial and five mixed. In 214 Stage III patients the 5-year overall survival rate was 44%, which compares favorably with the reported surgical rate of 20-25%. In both populations, the induction of DTH to unmodified autologous tumor cells was associated with significantly longer survival. This is a platform technology that is adaptable to other human cancers and early trials indicate immunological activity in ovarian and renal cell carcinomas.
Department of Medicine, Kimmel Cancer Center, Thomas Jefferson University, 1015 Walnut Street, Suite 1024, PA 19107, USA. d_berd@mail.jci.tju.edu
David
D
Berd
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D002986:Clinical Trials as Topic; D004136:Dinitrobenzenes / Q000276:immunology*; D006241:Haptens / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004136:Dinitrobenzenes; D006241:Haptens