TRA-8 illustration

  UAB researcher Tong Zhou’s illustration
  shows how TRA-8 kills cancer cells.

UAB-Daiichi Sankyo Program Advancing Promising Cancer Therapeutic Through Clinical Trials

In 1994, UAB entered into a sponsored research agreement with Sankyo Co., Ltd., that has led to the development of a monoclonal antibody directed toward a cell death receptor. Through the ongoing efforts of researchers at Sankyo and UAB, a promising therapeutic for cancer has emerged. Exclusive rights to these technologies were licensed to Sankyo by The UAB Research Foundation (UABRF) in 2003.

The key to this effort has been TRA-8, a mouse monoclonal antibody that binds death receptor 5 (DR5) and that was created by researchers at UAB and patented (U.S. Patent No. 7,476,383) by UABRF. TRA-8 activates cells that express DR5 and thereby induces apoptosis, or programmed cell death, of these cells. Cells that express DR5 include cancer cells and certain cells within the immune system. The complex mechanism whereby DR5 transmits its cell-killing signal is still under study. TRA-8 has been shown to kill tumor cells in animal models and also has potential for use in the treatment of diseases of the immune system, including rheumatoid arthritis and lupus.

Of significant importance, UAB and Sankyo investigators reported in 2001 (Ichikawa, et al., Nature Medicine 7:954-960, 2001) that TRA-8 is not hepatotoxic. This result suggested that TRA-8 was a promising drug candidate. Sankyo’s researchers have humanized the TRA-8 monoclonal antibody to enhance its usefulness in the treatment of human disease and have demonstrated that the humanized antibody, CS-1008, also does not exhibit hepatotoxicity (Yada, et al., Annals of Oncology 19:1060-1067, 2008).

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The relationship between Sankyo and UAB has been a productive one that recently has moved into the conduct of clinical trials. This relationship expanded in 2005 when a new Tokyo-based company, Daiichi Sankyo Co., Ltd., resulted from the merger of Sankyo with another Japanese pharmaceutical firm, Daiichi Pharmaceutical Co., Ltd. American operations were merged into Daiichi Sankyo’s U.S. headquarters in Parsippany, New Jersey. The company’s clinical development division in Edison, New Jersey, oversees clinical trials being conducted in the United States, the European Union, and other western countries. In recent years UAB’s scientists have been interacting with Daiichi Sankyo representatives in Japan as well as in the United States.

Daiichi Sankyo recently completed an open-label Phase I study of CS-1008 in patients with advanced solid malignancies and lymphomas. The promising results from this study were presented in a poster at the 2008 ASCO meeting (Selah, et al., J. Clinical Oncology, 26:3537, 2008), and the potency of CS-1008 against various tumor types now has been investigated in Phase II clinical trials. The UAB-Daiichi Sankyo Research Program is managed through an agreement with the Division of Rheumatology and Clinical Immunology in the UAB School of Medicine and the Comprehensive Cancer Center.  The ongoing relationship with Daiichi Sankyo is one of the largest industry-funded research programs at UAB. Key investigators who have developed this program in concert with Daiichi Sankyo include William Koopman, M.D.; Robert Kimberly, M.D.; Al LoBuglio, M.D.; Tong Zhou, M.D.; and Donald Buchsbaum, Ph.D.

Posted on 9/15/2009 12:10:00 PM