Hutch News Stories

Press brings cancer-fighting antibody work to Hutch

Drs. Oliver Press and Jinjuan Wang
Drs. Oliver Press and Jinjuan Wang, research scientist, pause while reviewing a gel demonstrating expression of a chimeric anti-CD20 T-cell receptor. Photo by Theresa Naujack

Dr. Oliver Press, a longtime collaborator with the Targeted Immunotherapy Group at the Hutch, has joined the faculty of the Clinical Research Division.

Press moved his laboratory to the Hutch from the Department of Medicine at the University of Washington Division of Oncology in January.

"We anticipate his move will enhance already successful collaborations," said Dr. Fred Appelbaum, director of the Clinical Research Division and an investigator in the Targeted Immunotherapy Group.

"I expect many faculty members to benefit from his presence here at the Hutch."

Antibody tests

Press' laboratory develops and tests molecules called antibodies that recognize and bind to proteins on the surface of immune system cells called B lymphocytes, interfering with the normal process of cell growth and differentiation and resulting in death of the cell.

Many surface proteins in B cells are abundantly expressed in B-cell lymphomas. A promising antibody target is the CD20 protein present on the B cell surface, and it is involved in the regulation of B-cell proliferation and differentiation. By binding an antibody to CD20, cell proliferation and differentiation can be disrupted, resulting in cell death and tumor regression.

Collaborative studies between Press and Dr. Pat Stayton in the UW Department of Bioengineering involve genetic engineering to design superior antibodies to specific B cell surface proteins and the antibody conjugates.

Blinding efficiency

"Once an antibody is designed to target a specific cell surface protein, it is tested for binding efficiency in the laboratory, using cells in culture," Press said. "Promising antibodies are then tested in mice that bear lymphomas before the antibodies move to the clinic."

The breadth of Press' work impresses Appelbaum.

"It is unusual for one investigator to design a therapy, test it in a laboratory setting and follow it all the way to the clinic," he said. "Dr. Press is an unique investigator involved in all aspects of research, from basic cell science to pre-clinical and clinical trials."

Results obtained from cell-culture studies, animal-tumor models and early clinical trials led by Press and collaborators from the Targeted Immunotherapy Group suggest that the binding of the anti-CD20 monoclonal antibody disrupts normal communication in the lymphoma cells, contributing to tumor regression by inhibiting cellular growth or inducing cell death.

High response rate

In addition, selective targeting of radioactively tagged antibodies against CD20 permits tumor-specific delivery of radiotherapy. Clinical trials using such antibodies have shown a high response rate- 90 to 95 percent of B cell lymphoma patients treated with this therapy experience complete shrinkage of the tumor.

B-cell lymphoma is the fifth most common type of cancer, with 60,000 new cases reported each year. While there are other forms of non-Hodgkin's lymphoma, 85 percent of all lymphomas are B-cell specific.

"Antibody therapy, while designed specifically for B-cell lymphomas, can be used for the rarer Hodgkin's lymphoma due to infiltration of B cells in the tumor," Press said.

Collaborative studies

With members of the Targeted Immunotherapy Group, which include Appelbaum and Drs. Irwin Bernstein, Dana Matthews and David Maloney, Press is collaborating in studies to test radiolabeled antibodies targeting the CD19, CD20, CD33, and CD45 proteins in patients with relapsed leukemias and non-Hodgkin's lymphomas.

"This is an exciting time to be in Seattle doing cancer research, with the opening of the Seattle Cancer Care Alliance," Press said.

"The Hutch is developing an outstanding cancer center with the involvement of Children's Hospital and Regional Medical Center and the University of Washington."

Press will treat Alliance patients and maintain a joint appointment as professor in the UW Division of Oncology. Press holds a doctorate in biological structure and an MD with a specialty in oncology from the UW.

[Dr. Karen Spratt is a postdoctoral fellow in the Kemp lab of the Human Biology Division.]

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