Barbara Ann Karmanos Cancer Institute Researchers Show Phase I Immunotherapy with Armed T Cells Improve Overall Survival of Metastatic Breast Cancer Patients

CHICAGO, June 1 /PRNewswire/ -- Researchers at the Barbara Ann Karmanos Cancer Institute in Detroit today presented findings that show immunotherapy with armed targeted T cells may improve the overall survival of women with metastatic breast cancer.

(Logo:

http://www.newscom.com/cgi-bin/prnh/20071106/KARMANOSCANCERINSTITUTELOGO )

Abstract 3034, Phase I immunotherapy in women with metastatic breast cancer with activated T cells targeted with anti-CD-3 x anti-Her2/neu bispecific antibody, was given at the American Society of Clinical Oncology Annual Meeting in Chicago.

The study's goal was to determine whether the patients' T cells, armed with an antibody, could be expanded and used safely to attack the tumor, said Lawrence Lum, M.D., D.Sc., Scientific Director of BMT and Immunotherapy, Professor of Medicine at Karmanos Cancer Institute and the Wayne State University School of Medicine.

According to Dr. Lum, preclinical studies showed that anti-CD3 activated T cells (ATC) can be expanded and retargeted or armed with anti-CD3x anti-Her2 bispecific antibody (HER2Bi). The studies demonstrated that Her2B-armed ATC expand, divide, and exhibit high levels of cytotoxicity directed at breast cancer cells and secrete cytokines essential for boosting immune responses to tumors.

Seventeen patients, aged 31 - 86, were treated with eight infusions twice a week for four weeks with 5, 10, 20 and 40 billion ATC doses (armed with Her2Bi) to determine the maximum dosage tolerated. T cells from leukopheresis were activated and expanded with anti-CD3/IL-2 for 14 days, harvested, armed with Her2Bi, and cryopreserved. IL-2 (3 x 105 IU/m2/daily) and GM-CSF (250 micrograms/m2 twice a week) were given three days prior to the first infusion and ended one week after the last infusion.

"The results suggest that this treatment modality may improve overall survival for metastatic breast cancer," Dr. Lum said. "Although high numbers of remissions were not induced, we may have improved the patients' longevity and quality of life without undue toxicities. The predominant side effects were chills, fever, headaches, and transient hypotension that were controlled with medications and fluid support."

"It appears that infusions of targeted T cells have boosted the immune system to create a more efficient tumor killing machine within the patient's body," he said. "Although the median survival rate for all patients remains undefined, survival rates for the HER2 (0-2+) cohort is 21.3 months." He said that the immunotherapy may be vaccinating the patient's immune system to their own tumors. This is encouraging given that the tumor burden was high in the majority of women who had failed other therapies and the prognosis is poor.

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, Boston University, 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 team Voravit Ratanatharathorn, M.D. and Joseph Uberti, M.D., Ph.D.

The Phase I Clinical Trial was supported by a National Cancer Institute ROI CA92344 grant, a translational grant from the Leukemia & Lymphoma Society Michigan Life Science Grant, funds from Roger Williams Hospital, Providence RI and funds from the Karmanos Cancer Institute.

The Barbara Ann Karmanos Cancer Institute

The Barbara Ann Karmanos Cancer Institute in Detroit is one of 41 National Cancer Institute (NCI)-designated comprehensive cancer centers in the United States. Caring for more than 6,000 new patients annually on a budget of $216 million, conducting more than 700 cancer-specific scientific investigation programs and clinical trials, the Karmanos Cancer Institute is among the nation's best cancer centers. Its Phase I Clinical Trials Program is one of only 16 NCI funded programs in the country. Through the commitment of 1,000 staff, including nearly 300 faculty members, and supported by thousands of volunteer and financial donors, the Institute strives to prevent, detect and eradicate all forms of cancer. John C. Ruckdeschel, M.D., is the Institute's president and chief executive officer. For more information call 1-800-KARMANOS or go to www.karmanos.org.

American Society of Clinical Oncology

ASCO is the world's leading professional organization representing physicians who care for people with cancer. With more than 25,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. For ASCO information and resources, visit www.asco.org/presscenter.

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