Technology evaluation: Theratope, Biomira Inc.
Active specific immunotherapy, the use of 'vaccines' to stimulate therapeutic tumor antigen-specific immune responses, holds promise as a complementary approach to chemotherapy, radiation and surgery for the treatment of patients with cancers that have a high risk of relapse or progressive disease. Important components of an agent used for active immunotherapy are immunogens in the form of tumor-associated antigen(s) and an adjuvant or carrier molecule to promote presentation of the antigen to the immune effector cells. Possible antigens include tumor-expressed proteins or carbohydrate structures such as the glycoprotein mucin and its epitopes. The Theratope vaccine, consisting of a synthetic mimic of the mucin-associated glycan epitope STn conjugated to the carrier molecule keyhole limpet hemocyanin, has been developed for immunizing patients with mucin-expressing tumors. In murine and human studies, the vaccine has been shown to stimulate anti-STn antibodies and mucin-specific T-cell responses. The immune response is augmented by pretreatment with intravenous cyclophosphamide that serves to inhibit suppressor T-cells. Phase II studies suggested a survival benefit for breast cancer patients who received the Theratope vaccine after intravenous cyclophosphamide. A multinational phase III study testing the Theratope vaccine in patients with metastatic breast cancer who have had a clinical response or stability of disease is ongoing. Other malignancies for which the vaccine may be applicable include ovarian and gastrointestinal cancers.
Duke University Medical Center, Department of Surgery, Immunology and Pathology, Durham, NC 27710, USA. m.morse@cgct.duke.edu
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D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology / Q000627:therapeutic use*; D001709:Biotechnology; D001943:Breast Neoplasms / Q000628:therapy; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006433:Hemocyanins / Q000627:therapeutic use; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; C055491:sialosyl-Tn antigen; C099077:sialyl-Tn antigen-keyhole-limpet hemocyanin conjugate; D006433:Hemocyanins