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http://www.newscom.com/cgi-bin/prnh/20071106/KARMANOSCANCERINSTITUTELOGO )
Abstract 3034, Phase I immunotherapy in women with metastatic breastcancer with activated T cells targeted with anti-CD-3 x anti-Her2/neubispecific antibody, was given at the American Society of Clinical OncologyAnnual Meeting in Chicago.
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The study's goal was to determine whether the patients' T cells, armedwith an antibody, could be expanded and used safely to attack the tumor, saidLawrence Lum, M.D., D.Sc., Scientific Director of BMT and Immunotherapy,Professor of Medicine at Karmanos Cancer Institute and the Wayne StateUniversity School of Medicine.
According to Dr. Lum, preclinical studies showed that anti-CD3 activated Tcells (ATC) can be expanded and retargeted or armed with anti-CD3x anti-Her2bispecific antibody (HER2Bi). The studies demonstrated that Her2B-armed ATCexpand, divide, and exhibit high levels of cytotoxicity directed at breastcancer cells and secrete cytokines essential for boosting immune responses totumors.
Seventeen patients, aged 31 - 86, were treated with eight infusions twicea week for four weeks with 5, 10, 20 and 40 billion ATC doses (armed withHer2Bi) to determine the maximum dosage tolerated. T cells from leukopheresiswere activated and expanded with anti-CD3/IL-2 for 14 days, harvested, armedwith Her2Bi, and cryopreserved. IL-2 (3 x 105 IU/m2/daily) and GM-CSF (250micrograms/m2 twice a week) were given three days prior to the first infusionand ended one week after the last infusion.
"The results suggest that this treatment modality may improve overallsurvival for metastatic breast cancer," Dr. Lum said. "Although high numbersof remissions were not induced, we may have improved the patients' longevityand quality of life without undue toxicities. The predominant side effectswere chills, fever, headaches, and transient hypotension that were controlledwith medications and fluid support."
"It appears that infusions of targeted T cells have boosted the immunesystem to create a more efficient tumor killing machine within the patient'sbody," he said. "Although the median survival rate for all patients remainsundefined, survival rates for the HER2 (0-2+) cohort is 21.3 months." Hesaid that the immunotherapy may be vaccinating the patient's immune system totheir own tumors. This is encouraging given that the tumor burden was high inthe majority of women who had failed other therapies and the prognosis ispoor.
In addition to Dr. Lum, abstract authors include: Zaid Al-Kadhimi, M.D.,Associate Director of Immunotherapy, Karmanos Cancer Institute; Cassara Skuba,B.S., Supervisor of Cell Processing Facility, Karmanos Cancer Institute;Rebecca Sandborg, Ph.D., Karmanos Cancer Institute; Ritesh Rathore, M.D.,Chief of Hematology/Oncology, Assistant Professor of Medicine, BostonUniversity, Roger Williams Hospital, Providence, RI; Qin Liu, Ph.D.,Assistant Professor of Medicine, University of Massachusetts, Worcester, MA;and Co-Leaders of the Karmanos Cancer Center BMT Multidisciplinary teamVoravit Ratanatharathorn, M.D. and Joseph Uberti, M.D., Ph.D.
The Phase I Clinical Trial was supported by a National Cancer InstituteROI CA92344 grant, a translational grant from the Leukemia & Lymphoma SocietyMichigan Life Science Grant, funds from Roger Williams Hospital, Providence RIand funds from the Karmanos Cancer Institute.
The Barbara Ann Karmanos Cancer Institute
The Barbara Ann Karmanos Cancer Institute in Detroit is one of 41 NationalCancer Institute (NCI)-designated comprehensive cancer centers in the UnitedStates. Caring for more than 6,00
