Antibody Program Meeting

A meeting of the LICR Antibody Program, the world’s largest academic therapeutic antibody program, was held in the New York Office on September 22, 2003. The scientists and clinicians coordinating each of the seven principal components (see Figure) gathered to report progress within the Program, a highly-integrated and truly global enterprise. Very brief summaries of the reports are given below.

Following an introduction by Dr. Lloyd J. Old, the Scientific Director and CEO of the LICR, and the principal coordinator of the Antibody Program, the meeting began with a summary report, from Dr. Eric W. Hoffman (Director, Office of Clinical Trials Management), of the active and planned clinical programs centered on the antibodies 3S193, A33, and 806. To date, 14 studies have been completed, with approximately 300 patients having been treated.

Drs. Gerd Ritter, Matt Scanlan, and Achim Jungbluth from the LICR New York Branch, together with Dr. Andrew J.G. Simpson (Director, James R. Kerr Program), summarized the process of antigen discovery and characterization, which is referred to as BITPH: bioinformatics, immunomics, transcriptomics, proteomics, and histiomics (histochemistry). Antigen discovery through bioinformatics has been greatly facilitated by the use of data derived, through the LICR Genomics Program, from the technologies of ORESTES (open reading frame expressed sequence tags){Dias, 2000 2763 /id}, which was developed at the LICR São Paulo Branch, and MPSS (massively parallel signature sequencing){Jongeneel, 2003 4072 /id} in an academic/commercial partnership with the National Cancer Institute (Maryland, USA), Duke University (North Carolina, USA), and Lynx Therapeutics (California, USA). The bioinformatic research associated with the Program has been led by Dr. Victor Jongeneel (Director, LICR Office of Information Technology) and his team. Cell surface antigen identification and antibody characterization for target validation are performed primarily at the LICR New York Branch, and increasingly use reagents generated by James R. Kerr Program Investigators Drs. Ivan Gout (Kyiv) and Bo-Quan Jin (Xi’an). This process was illustrated using a new antibody target, A34, identified in the New York Branch.

Antibody research and development work presented at the meeting included: light microscopy studies and live imaging from Drs. Derek Toomre and Ira Mellman (New Haven Affiliate Unit) revealing the localization, internalization and dynamics of the A33 antibody; epitope mapping of the 806 antibody resulting from a collaboration between Dr. K. Dane Wittrup (Massachusetts Institute of Technology, USA), and Drs. Terry Johns and Andrew Scott (Melbourne Branch); positron emission tomography (PET) program updates on radiolabelling studies to determine antibody targeting and pharmacokinetics by LICR Affiliates Drs. Steve Larsen, Chaitanya Divgi, and Ron Finn from the Memorial Sloan-Kettering Cancer Center (MSKCC), and Dr. Scott at the LICR Melbourne Branch/Austin Hospital; clinical trials using G250 as a radioimmunotherapy were reported by LICR Affiliates Drs. Egbert Oosterwijk (Nijmegen) and Divgi (MSKCC); and a newly established collaboration with clinical investigators at the University of Uppsala (Sweden) was reported by Dr. Divgi.

In the context of the generation of humanized constructs suitable for clinical application, Drs. Ritter and Christoph Renner (Homburg Affiliate Center) gave a progress report on antibody engineering being performed at the New York Branch, with the Homburg and Lausanne (by Dr. Florian Wurm) Affiliate Centers, and with commercial partners. In addition, Drs. Carl Batt (Ithaca Affiliate Center) and Scott (LICR Melbourne Branch) also discussed the work on construct generation and engineering, and gave overviews of the work-to-date and current status of the Biological Production Facilities at their respective centers.

The commercial status and licensing opportunities for the Antibody Program were reported by Drs. Robert Burns (Director, LICR Office of Technology Licensing) and Pär Olsson (LICR Office of Intellectual Property). The meeting finished with an extensive round-table discussion, led by Dr. Old, regarding the portfolio of candidates, constructs and cytotoxic agents.

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