UChicago, partners collaborate with industry to develop next-generation cancer therapies

A new collaboration between Celgene Corp. and the Recombinant Antibody Network, a consortium comprising research groups from the University of California-San Francisco, the University of Chicago and the University of Toronto, will support the development of next-generation, antibody-based cancer therapies.

In this first industry partnership for the network, Celgene agreed to pay $25 million for the option to enter into future license agreements to develop and commercialize promising therapeutic antibodies to cancer-related targets.

“The RAN consortium has developed an automated, antibody engineering pipeline that enables high-throughput generation and validation of high-performance recombinant antibodies, at an unprecedented scale,” said James Wells, one of the network’s founding members and a professor of pharmaceutical chemistry in the UCSF School of Pharmacy. “This is a unique opportunity to partner with a top biopharmaceutical company to exploit these capabilities on extracellular targets in the discovery and development of new therapies for treating cancer.”

Over the past decade, antibodies have emerged as the major breakthrough in targeted cancer therapy and are now the fastest growing class of therapeutic molecules. Unfortunately, antibody development remains an imprecise science, conducted on a case-by-case basis.

To address the unmet need for an efficient pipeline for renewable antibody discovery, Wells co-founded the network with two other veterans from the former Protein Engineering Department at Genentech Inc. Sachdev Sidhu, now a professor of molecular genetics at the University of Toronto, and Anthony Kossiakoff, a professor of biochemistry and molecular biology at the University of Chicago, have teamed with Wells to make automated, large-scale antibody production a reality. The network generates recombinant antibodies from cloned synthetic genes that are selected for high performance.

“We created the RAN to address a large, unmet need in both research tools and therapeutic antibody development,” said Kossiakoff. “The RAN will continue to solve the problems that are inherent in traditional antibody approaches, and help to expand treatments for a variety of diseases, including cancer.”

During the past decade, the researchers have developed new methods to rapidly and reliably produce large libraries of recombinant antibodies, which are tailored, synthetic antibodies created in vitro that consistently show high performance. Using funding from the National Institutes of Health, the network has completed an ambitious project that has provided thousands of high-quality antibodies targeting hundreds of human transcription factors—the signaling molecules that cells use to control when and how their genes produce proteins, which previously have been particularly challenging to target with antibodies. The robotic network system enables researchers to select these antibodies efficiently at a broad scale to begin to approach the level of the proteome, the full system of proteins found in a human or organism.

“We look to this collaboration with RAN as a key element of our commitment to discovery and development of innovative and impactful bio-therapeutics,” said Thomas Daniel, president of Celgene Research and Early Development. “Coupled with other key collaborations in the biologics space, we expect RAN to deliver great value identifying and validating important antibody targets in our areas of current therapeutic focus and beyond.”

The collaboration with Celgene enables the network to use its systematic approach to signaling proteins on the cell’s surface that drive cancer and immunological disease to develop specific licensing opportunities. The network also will leverage collaborations with academic groups to engineer antibodies for basic biological research and for developing novel treatments for cancer and other devastating diseases.

“Through this partnership, we are taking a giant step forward in the ultimate goal of the RAN: the systematic targeting of the “extra-cellularome,” the cell-surface proteins that control cancer and other diseases,” said Sidhu, who leads the University of Toronto’s Centre for the Commercialization of Antibodies and Biologics. “In the future, we envision that we will be able to precisely target cancer cells at the molecular level, which will provide better therapies for patients.”