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Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

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Annual summary rept. 11 Aug 2004-10 Aug 2005

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This grant supports studies to understand the potential of universal tumor antigens for cancer immunotherapy, with a particular focus on the characterization of the human telomerase reverse transcriptase hTERT as tumor antigen. Telomerase is expressed by 90 of all human breast cancers but absent in most normal cells. Telomerase function has been directly linked to oncogenesis and its inhibition in telomerase-positive human tumors leads to growth arrest. Following a series of published in vitro preclinical experiments, we are now testing the hypothesis of telomerase as a tumor rejection antigen in vivo in humans. This year we completed enrollment in the dose escalation portion of our hTERT peptide vaccine trial. Immunologic responses were assessed and the optimal dose level was chosen and an additional four patients were treated at that dose. Furthermore, we have initiated work examining the role of intravenous cyclophosphamide prior to hTERT vaccination in an attempt to boost vaccine response by depleting regulatory T cells. Data thus far from our past and current trials suggest that telomerase peptide vaccination is biologically active and leads to in vivo immune recognition of carcinoma by effector lymphocytes and tumor necrosis.

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  • Anatomy and Physiology
  • Medicine and Medical Research
  • Pharmacology

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