Albert B. Deisseroth, MD, PhD

2007-2008 BCRF Project:
A vaccine composed of subcutaneous injections of an Ad-sig-hMUC-1/ecdCD40L vector prime-hMUC-1/ecdCD40L protein boost (the hMUC-1/ecdCD40L VPP vaccine) is being prepared for phase I clinical trial testing. The vaccine attaches MUC-1, which is known to promote metastasis and chemotherapy resistance in breast cancer, to the CD40 ligand (CD40L), which is a potent immuno-stimulatory signal present in CD4 helper cells, which is essential to the activation of antibody production and cellular immune response against the breast cancer cells.

The presence of the CD40L in this vaccine accomplishes two things. It replaces the CD40L signal which is missing in the CD4 cells of individuals above the age of 55 years, thereby making the vaccine strategy successful in the older individuals. It also delivers the hMUC-1 tumor antigen to the dendritic cells (DCs) which are important to activation of the immune response. This vaccine is unique in that it is designed to work in women above the age of 55 years, whereas most vaccines tested do not induce an immune response in the older age groups. Recently, it has been reported that the target of this vaccine, MUC-1, is a marker for the breast cancer tumor stem cell. The tumor stem cells is a very rare or low frequency cell in the tumor cell population, which is very resistant to chemotherapy and radiation, and is constantly producing new tumor cells. It is possible that the vaccine will destroy the most aggressive part of the breast cancer cell population, which contribute to relapse, the tumor stem cells. The immune response induced by the vaccine develops within 21 days and lasts over a year. It can be boosted by injections of the MUC-1/ecdCD40L protein.

This vaccine will be used to decrease recurrence in women at high risk of recurrence after surgery and conventional adjuvant therapy. The trial is now scheduled to begin in August, 2007. This is the very first vaccine trial conducted to be directed to the destruction of the breast cancer stem cell. As such, it has the potential to reduce recurrence after initial therapy and to induce regressions at the time of recurrence.

Mid-Year Progress Report:
Dr. Deisseroth reports that as a result of BCRF support, his vaccine is ready to go into the clinic. The FDA gave permission for patient entry on this protocol on December 7, 2007. The vaccine will be tested in women who have recurred after surgery and conventional adjuvant therapy, who have received frontline salvage therapy, and who have stable disease while being treated with any of the following agents: Herceptin, tamoxifen, raloxifene or biphosphanates. Patients who have developed a partial response following recurrence and are on any of the agents listed previously, are eligible as long as their tumor markers are stable for a period of three months. The trial will start later in February and Dr. Deisseroth projects accrual of 12 patients by September 30, 2008.

Bio:
Dr. Albert Deisseroth is best known for the development of new directions in the treatment of leukemias and solid tumors through the use of molecular targeting and genetic therapy. He has also been active in the development of new targeting and genetic modification techniques for the treatment of solid tumors. This work has led to a cancer vaccine that can induce T cell mediated immunity against tumor associated antigens for up to a year in animal models. This work has also led to vectors which can target chemotherapy so as to decrease toxicity and increase the efficacy of combination chemotherapy. Currently he is launching a vector mediated tumor vascular targeting trial for breast cancer among other malignancies.

Dr. Deisseroth is currently the President and CEO of the Sidney Kimmel Cancer Center in San Diego, CA. Dr. Deisseroth received his M.D. in 1970 and Ph.D. in 1968 from the University of Rochester School of Medicine in Rochester, New York. He completed his internship and residency at Beth Israel Hospital in Boston and was a Fellow in Medicine at Harvard Medical School. Following several years of training at the NIH and at the Dana Farber Cancer Center, Dr. Deisseroth joined the Pediatric Oncology Branch of the NCI as Head of the Experiment Hematology Section.

Other positions held by Dr. Deisseroth include: Ensign Professor of Medicine, Chief of Medical Oncology, and Associate Director of the Yale Cancer Center at Yale University School of Medicine, the Anderson Professor of Cancer Treatment and Research and Chairman of the Department of Hematology at the UT MD Anderson Cancer Center, and Professor of Medicine at UCSF and Chief of the Medical Oncology/Hematology Division at the San Francisco VAMC.