Autologous, hapten-modified vaccine as a treatment for human cancers.
We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with BCG. Administration of DNP-vaccine to patients with metastatic melanoma induces a unique reaction - the development of inflammation in metastatic masses. Histologically, this consists of infiltration of T lymphocytes, most of which are CD8+. These T cells usually produce gamma interferon in situ. Moreover, they represent expansion of T cell clones with novel T cell receptor structures. Occasionally, administration of DNP-vaccine results in partial or complete regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the post-surgical adjuvant setting produces a more striking clinical effect. We have treated 214 patients with clinically evident stage III melanoma who had undergone lymphadenectomy. With a median follow-up time of 4.4 years (1.8-10.4 years) the 5-year overall survival (OS) rate is 47% (one nodal site = 51%, two nodal sites = 33%). These results appear to be comparable to those obtained with high dose interferon. More recent studies suggest that this therapeutic approach is also applicable to ovarian cancer. There appear to be no insurmountable impediments to applying this approach to much larger numbers of patients or to developing it as a standard cancer treatment.
Department of Medicine, Division of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA. d_berd@lac.jci.tju.edu
D
D
Berd
D000951:Antigens, Neoplasm / Q000627:therapeutic use; D001324:Autoantigens / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004136:Dinitrobenzenes; D005260:Female; D006241:Haptens; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy
D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D004136:Dinitrobenzenes; D006241:Haptens