By Vicki Brower

Special To BioWorld Today

Two privately held companies formed barely a year ago, CDR Therapeutics Inc. and CellGenEx Inc., have merged, forming Xcyte Therapies Inc., which will focus on antibody-based treatments for immune system disorders, infectious diseases and cancer.

Xcyte will be based in Seattle, where CDR Therapeutics is located, and will develop drugs that target cell surface receptors linked to immunoregulation.

To help finance the new venture, Xcyte raised $4.1 million in private equity funding from four venture capital firms that helped found CDR Therapeutics in August 1996: ARCH Venture Partners, the development arm of the University of Chicago; The Sprout Group, of Menlo Park, Calif.; Alta Partners, of San Francisco; and Sofinnova, of Paris.

CDR Therapeutics and CellGenEx, of Chicago, shared a personal and investment past, as well as common vision, said Xcyte president and CEO, Ronald Berenson, a founder of CDR Therapeutics and before that, of CellPro Inc., of Bothell, Wash.

ARCH's Robert Nelsen founded CellGenEx, and two other founders of CDR Therapeutics, Carl June and Craig Thompson, worked at the Fred Hutchinson Cancer Center, in Seattle, with Berenson in the mid-1980s. A number of Xcyte's scientists were involved in discovering key immune system receptors, which the new company is utilizing for its antibody engineering platform.

Most importantly, however, the two companies' collective know-how in immunology meshed well. Xcyte brings together scientists and technologies which translate into several products that target receptors, either down- or up- regulating immune responses.

Jeff Bluestone, from the University of Chicago, developed a method to activate T cells using anti-CD3 antibodies. Bluestone has demonstrated in preclinical studies that antibodies that bind to the CD3 complex receptor can be used to stimulate cellular immune responses in cancer and infectious diseases; clinical responses also were seen in a number of patients with few side effects. He also is developing other antibodies for selective immunosuppression.

Another therapeutic approach, ex vivo activated CD4+ T cells, was developed by June and Thompson. Based on their observations on the key role played by CD3 and CD28 receptors in activating T cells, they developed a technique to activate CD4+ cells ex vivo using a combination of antibodies to CD3 and CD28 cells, which are highly resistant to HIV. They published their results in a June 1997 issue of Science.

This technology is being tested in a pilot study on HIV-positive patients who are being given AZT, in an attempt to boost their immune responses. The therapy also is being tested in a pilot study in cancer patients.

In addition, Xcyte is creating small synthetic complementarity-determining region (CDR) molecules that simulate activity of monoclonal antibodies, but have advantages the antibodies don't have due to their large size, such as the ability to better penetrate tumors.

Xcyte's smaller molecules mimic the key binding sites — CDRs — of monoclonal antibodies. By designing such compounds, Mark Greene, of the University of Pennsylvania and another founder of CDR Therapeutics, has created CDR mimics to several different targets.

One new molecule, Mim erbB, binds to the Her2 receptor, which is overexpressed in many types of cancer, including breast, ovarian, lung, pancreatic and prostate. A mimic of a Her2/neu monoclonal antibody, Mim erbB down-regulates Her2 to normal levels, shutting off the proliferative signal and restoring normalcy to cancer cells, Berenson said. Mim erbB recently has been shown to act in synergy with chemotherapeutics such as cisplatin to arrest tumor growth.

Xcyte now is testing Mim erbB in preclinical studies and expects it to be superior to anti-Her2 antibodies for cancer treatment because its small size allows it to penetrate tumors more efficiently than the larger monoclonal antibodies. Initial clinical trials with Mim erbB will target breast cancer.

Xcyte's business plan is to focus initially on research and early development of its lead products and to select corporate partners for late-stage development, manufacturing, marketing and sales. Longer term, Xcyte expects to develop its own drugs.

The company has 20 employees and anticipates adding five to 10 staffers by the end of this year and 10 in 1998. Some new employees have come from New York-based Bristol-Myers Squibb Co.'s Seattle biotechnology operation, which recently was discontinued. *