作者: Miles, David ; Taylor-Papadimitriou, Joyce ; Baudin, Martine ; Acres, Bruce ; Van Belle, S. ; von Mensdorff-Pouilly, Silvia ; Squiban, Patrick ; Beuzeboc, Philippe ; Uzielly, B. ; Bizouarne, Nadine ; Scholl, Susy ; Shearer, Moira ; Pouillart, Pierre

MUC1 is expressed by glandular epithelial cells. It is overexpressed in the majority of breast tumours, making it a potential target for immune therapy. The objectives of the present study were to evaluate the anti‐tumour activity and tolerance of repeated administration of TG1031 (an attenuated recombinant vaccinia virus containing sequences coding for human MUC1 and the immune stimulatory cytokine IL‐2) in patients with MUC1‐positive metastatic breast cancer. This was an open‐label, randomised study comparing two dose levels, 5 × 10E6 and 5 × 10E7 pfu, with 14 patients in each arm. The treatment was administered intramuscularly every 3 weeks for the first 4 doses and every 6 weeks thereafter, until progression. Two patients had a partial tumour regression (>50%), and 15 patients had stable disease as their best overall response until at least the 5th injection. Partial regression lasted for 11 months in one patient and for 12 months in the second patient who then underwent surgical resection of her hepatic metastases. The most frequent adverse events included inflammation at injection site: 7 patients, itching or pain at injection site: 5 patients, and moderate fever: 6 patients. One responding patient developed antinuclear, anti‐DNA, and increased anti‐TPO antibodies after the fifth injection, and which resolved at the end of treatment. The treatment regimes were well tolerated with a low toxicity profile. Although clinical efficacy remains limited, this study demonstrates the potential use of MUC1‐based immune therapy in breast cancer.

2000-09-01·Journal of Immunotherapy4区 · 医学

Recombinant Vaccinia Virus Encoding Human MUC1 and IL2 as Immunotherapy in Patients With Breast Cancer

4区 · 医学

Article

作者: Fridman, Wolf ; Scholl, Susy M. ; Balloul, Jean-Marc ; Acres, Bruce ; Bizouarne, Nadine ; Pouillart, Pierre ; Deneux, Laurent ; Vincent-Salomon, Anne ; Von Mensdorff-Pouilly, Sylvia ; Schatz, Christian ; Tartour, Eric ; Kieny, Marie Paule ; Le Goc, Gwenaelle

Polymorphic epithelial mucin, encoded by the MUC1 gene, is present at the apical surface of glandular epithelial cells. It is over-expressed and aberrantly glycosylated in most breast tumors, resulting in an antigenically distinct molecule and a potential target for immunotherapy. This transmembrane protein, when produced by tumor cells, is often cleaved into the circulation, where it is detectable as a tumor marker (CA 15.3) by various antibodies, allowing for early detection of recurrences and evaluation of treatment efficacy. The objective of the current study was to examine the clinical and environmental safety and immunogenicity of a live recombinant vaccinia virus expressing the human MUC1 and IL2 genes (VV TG5058), referred to here as TG1031. The study was an open-label phase 1 and 2 trial in nine patients with advanced inoperable breast cancer recurrences to the chest wall. The patients were vaccinated intramuscularly with a single dose of TG1031; three patients were treated at each of three progressive dose levels ranging from 5x10(5) to 5x10(7) plaque-forming units. A boost injection at their original dose level was administered in patients responding immunologically, clinically, or both. Vaccination resulted in no significant clinical adverse effects, and there was no environmental contamination by live TG1031. All patients had been vaccinated as children, and patients treated at the highest dose level mounted a significant anti-vaccinia antibody response. None of the nine patients had a significant increase in MUC1-specific antibody titers after one single injection, whereas five patients had a detectable increase in vaccinia virus antibody titers. Peripheral blood mononuclear cells of one patient at the intermediate dose level showed a proliferative response to in vitro culture with vaccinia virus, with a stimulation index of 6. A second patient treated at the intermediate dose level had a stimulation index of 7 to MUC1 peptide and of 14 after a boost injection. This patient had a concomitant decrease in carcinoembryonic antigen serum levels and remained clinically stable for 10 weeks. Evidence of MUC1-specific cytotoxic T lymphocytes was detected in two patients. Immunohistochemical analysis revealed an increase in T memory cells (CD45RO) in tumor biopsies after vaccination. The absence of serious adverse events, together with the documentation of immune stimulations in vivo, warrant the further use of TG1031 in immunotherapy trials of breast cancer.

2000-02-01·Current opinion in molecular therapeutics

Technology evaluation: TG-1031, Transgene SA.

Review

作者: Jocham, D ; Doehn, C

Tumor-associated antigens have considerable promise not only as diagnostic or prognostic markers but also as targets for active or passive immunotherapy. The epithelial mucin MUC1 is a transmembrane molecule which is expressed by most glandular epithelial cells. Transgene has developed VV-MUC1-IL-2 (TG-1031), an antigen-specific therapy, involving the tumor antigen MUC1 and the cytokine IL-2 combined with a vaccinia virus vector. Vaccinia virus vectors have been shown to stimulate a strong immune response to encoded antigens in vivo. This therapy has potential for the treatment of breast cancer, prostate cancer and other adenocarcinomas and is currently under investigation in phase I and II trials.

100 项与 TG-1031 相关的药物交易

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