dinitrobenzenes and Ovarian-Neoplasms

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.

Topics: Antigens, Neoplasm; Autoantigens; Cancer Vaccines; Combined Modality Therapy; Dinitrobenzenes; Female; Haptens; Humans; Inflammation; Lymphocytes, Tumor-Infiltrating; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms

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 interferon-gamma in situ. Moreover, they represent expansion of T-cell clones with novel T-cell receptor (TCR) structures. Occasionally, administration of DNP-vaccine results in regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the postsurgical adjuvant setting produces a more striking clinical effect. Of 62 patients with clinically evident stage III melanoma who had undergone lymphadenectomy, the 5-year relapse-free survival rate was 45% and the overall survival rate was 58%. These results appear to be better than those obtained with high-dose interferon, although a randomized phase III trial is required to prove that point. A recent phase I study suggests that this therapeutic approach is also applicable to stage III 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.

Topics: Animals; Cancer Vaccines; Clinical Trials as Topic; Dinitrobenzenes; Female; Haptens; Humans; Hypersensitivity, Delayed; Immunotherapy, Active; Inflammation; Lung Neoplasms; Male; Melanoma; Mycobacterium bovis; Neoplasm Metastasis; Ovarian Neoplasms; T-Lymphocytes; Tumor Cells, Cultured

Lysozyme was measured using the synthetic substrate 3',4-dinitrophenyl tetra-N-acetyl-beta-chitotetraoside and the LKB Reaction Rate Analyser. This method has been evaluated by comparing levels obtained with serum samples from healthy individuals and patients with either cancer or inflammatory bowel disease with those obtained from the same specimens using a turbidimetric method. In terms of standard egg-white lysozyme, the colorimetric method gave much higher levels for all samples than the turbidimetric method; however, similar group differences were maintained. For individual serum specimens significant correlation between the two methods was found to occur only in the healthy group. Assay precision for the two methods was similar but the turbidimetric method could detect levels of lysozyme activity which were 10 times lower than those detected by the colorimetric method.

Topics: Biological Assay; Chitin; Colitis, Ulcerative; Colorimetry; Crohn Disease; Dinitrobenzenes; Female; Humans; In Vitro Techniques; Micrococcus; Muramidase; Nephelometry and Turbidimetry; Ovarian Neoplasms