Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Glycopeptide vaccines for adenocarcinomas of the breast and ovary (Meeting abstract).
Society for Biological Therapy 1992 Annual Meeting: Biological and Immunological Treatments for Cancer. October 29-November 1, 1992, Williamsburg, VA, p. 31, 1992.. Unique Identifier : AIDSLINE ICDB/93690685 Longenecker BM; Univ. of Alberta, Edmonton, Alberta, Canada
Abstract:
We have developed a novel approach for ASI of carcinomas using synthetic carbohydrate, peptide and glycopeptide epitopes in immunotherapeutic vaccine formulations. Two Phase I clinical trials have been completed using a synthetic Thomsen-Friedenreich hapten conjugated to KLH (TF-KLH) + DETOX adjuvant in 12 ovarian cancer patients (pts) and sialyl-Tn (STn)-KLH + DETOX in 12 breast cancer pts. Specific humoral immune responses were noted, including a vigorous IgG response to the specific hapten against which the various pts were immunized. Complement-mediated cytotoxic antibodies which were specifically hapten-inhibitable against appropriate tumor cell targets developed in most of the pts following immunization. All of the ovarian cancer pts had extensive metastatic disease on entry into the trial. A significant correlation between CD4:CD8 ratios at trial entry and survival was noted in these pts. In both studies, an inverse correlation between CD4:CD8 ratios and numbers of CD8, CD57 double-positive cells (putative suppressor cells?) was noted. One of the ovarian cancer pts who was immunized with the STn-KLH formulation, after having completed her full course of TF-KLH immunizations, demonstrated a specific sequential humoral immune response to each hapten. Two of the breast cancer pts entered the trial with widespread disease, but the remaining 10 pts entered with minimal metastatic disease, with measurable metastatic lesions in all cases. 3/12 pts showed progressive disease despite ASI, including the 2 pts who had widespread disease on trial entry. Four pts have demonstrated stable disease for 7-12 mo since trial entry and 1 pt showed progressive disease after 8 mo of stable disease. Two pts showed a mixed response, both subsequently having disease progression. One pt had a good partial response for approx 7 mo, then showed progressive disease several months following her last ASI. One additional pt had a partial response, which has been maintained for approx 3 mo. Phase II/III studies will be required to confirm the efficacy of our synthetic ASI formulations. Carrier-free peptide and glycopeptide vaccines were synthesized which mimic putative MUC1 epitopes expressed on human breast carcinoma cells. An animal model for ASI using mouse adenocarcinoma cells transfected with the human MUC1 gene, which was developed in collaboration with Dr. Joyce Taylor-Papadimitriou and her colleagues at ICRF, London, was used to demonstrate effective ASI. Phase I clinical trials with these novel vaccines are now being planned.
Keywords: Adenocarcinoma/IMMUNOLOGY/*THERAPY Adjuvants, Immunologic Antibody Formation Antigens, Tumor-Associated, Carbohydrate/IMMUNOLOGY/THERAPEUTIC USE Breast Neoplasms/IMMUNOLOGY/*THERAPY CD4-CD8 Ratio Disaccharides/ADMINISTRATION & DOSAGE/IMMUNOLOGY Hemocyanin/ADMINISTRATION & DOSAGE/IMMUNOLOGY Human IgG/IMMUNOLOGY *Immunodominant Epitopes *Immunotherapy Mucins/IMMUNOLOGY Neoplasm Proteins/IMMUNOLOGY Ovarian Neoplasms/IMMUNOLOGY/*THERAPY ABSTRACT CLINICAL TRIAL, PHASE I 930830
M9380838
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
