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.
Morse
M A
MA
Duke University Medical Center, Department of Surgery, Immunology and Pathology, Durham, NC 27710, USA. m.morse@cgct.duke.edu
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