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HUPO Congress Opens in Montreal; Antibody Initiatives Lay Out Plans

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HUPO World Congress 2003 kicked off at the cavernous Palais des Congres in Montreal on Wednesday with a packed schedule of all-star speakers, including 2002 Nobel Prize winner John Fenn and HUPO president Sam Hanash.

In addition to the pomp and circumstance, opening day saw the first of a series of sessions that will update attendees on HUPO’s international initiatives. Speakers from Germany and China highlighted antibody projects that will fall under the umbrella of the HUPO antibody initiative. The scheduled first speaker, Mathias Uhlen — who has made waves with a Human Proteome Resource that is tentatively slated to play a major role in the initiative (see PM 9-5-03, PM 9-19-03) — posted a last minute cancellation. But Marius Ueffing of the German Society for Proteome Research, and leader of the European Proteome Initiative, gave a talk that laid out a map for a project to create a monoclonal antibody bank against recombinantly expressed human antigens, which is set to start in January 2004.

In Ueffing’s talk, which was laden with candid pleas for funding from big pharma and biotech, he defended his use of monoclonal antibodies, despite their lower throughput and greater cost than similar technologies. “Why use monoclonals? It is a well-established technology that is robust, reproducible, easy to handle, and reliable,” Ueffing said. He also said monoclonal antibodies, being free of IP claims, could generate “enormous value” once available in an accessible bank, partly because potential investors could then apply for IP on the applications that they invented using the antibodies. “Other technologies are not equally mature or are protected by IP,” Ueffing said.

The project will proceed in five steps. The first step will be the generation of cDNA, which Ueffing said could be accomplished largely by combining existing European sources. Step two, protein expression, is expected to be a bottleneck due to the difficulty the selected service centers are expected to have in expressing proteins such as integral membrane proteins. Step three will be the generation of monoclonal antibodies, which will take place at two facilities that have animal houses for antigen inoculation: one in Rijeka, Croatia — the country’s “first major biotech facility” (see PM 9-19-03) — and one at an as-yet-undecided location. The fourth step will be rigorous QC. Step five will be the maintenance of hybridoma cell lines.

Ueffing spent much of his talk throwing carrots to potential investors. “This database will generate value from its exploitation,” he said. He cited “relevance for pharma” as one of the top priorities of the project, and then listed myriad reasons for companies to find it relevant. In addition to the attraction of IP, he said that companies willing to fork over cash would be entitled to the generation of antibodies for their tissue or organ of choice; license-free, private access to the database; clones and cell lines for doing their own production; access to cDNA; antibodies at production cost; a chance to collectively decide upon 1,000 of the 2,000 central nervous system antigens for which antibodies will be made in the pilot project; and eventually, an opportunity to partake in what Ueffing predicted would be significant growth in the protein biochip market. “Ten years ago, Roche funded Affy to make cDNA chips,” Ueffing said. “Look at them now.”

Ueffing is suggesting that interested pharma companies invest a total of $7 million in the pilot phase of the project and $40 million in the next phase, which he anticipates will involve the generation of 10,000 specificities.

Qi-Hong Sun, an investigator at the Beijing Institute of Radiation Medicine, followed Ueffing’s lecture with a description of the Chinese HUPO Antibody Initiative, which has emerged as an arm of the HUPO Liver Proteome Project, a HUPO initiative based in Asia (see PM 8-18-03). The Chinese antibody team comes mainly from Sun’s lab and Fuchu He’s lab in Beijing, and labs at First Military Medical University in Guangzhou and the United Antibody Center in Shanghai.

The Chinese team’s goal is to set up a bridge between the HLPP and the Human Plasma Proteome Project. The investigators hope to initially develop two antibody banks: one composed of antibodies against all the antigens in the liver proteome, including plasma proteins secreted by the liver — which accounted for some 70 percent of all liver proteins, according to one experiment — and one against all plasma proteins that are unknown and are not secreted by the liver. The team’s strategy for generating the antibodies — termed subtractive immunization for tissue monoclonal antibody bank — differs from traditional immunization techniques, most importantly in that the starting point is fractionated proteins from homogenized tissue containing unknown antigens, rather than recombinant known antigens derived from the gene. Hybridoma lines are raised from the immunized animal as in traditional antibody generation, but when used with plasma antigens, the monoclonal antibodies are fractionated repetitively to remove those antibodies raised against albumin and other highly abundant plasma proteins.

The resulting monoclonal antibodies will be characterized in validation and localization studies using traditional immunohistochemistry and Western blot techniques, and the initial antigens can be pulled out this way for identification by mass spectrometry. Sun said that the advantage of the Chinese method was that the monoclonal antibodies were raised against native proteins while still being low cost and easy to make. He estimated that the group could generate “hundreds” of monoclonal antibodies a year using these techniques. He also hoped to eventually make arrays from the antibodies.

Although HUPO is sharing the event this year with the International Union of Biochemistry and Molecular Biology XIX World Congress — which cancelled a summer conference in Toronto due to the SARS epidemic — the organization stole the show when Hanash announced opening night that the HUPO Council had chosen Montreal as its headquarters. This led to speeches by local politicians and administrators who praised HUPO and its mission. HUPO also announced that its third annual World Congress will be held in October 2004 in Beijing.

— KAM

 

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