Subject: Cell Genesys Advances Creation of Disease-Fighting Antibodies 
Date: Published: 3/18/93 (82 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Technology & Medicine:
    Of Mice and Men:  Cell Genesys Advances
    Creation of Disease-Fighting Antibodies
    ----
    By Marilyn Chase
    Staff Reporter of The Wall Street Journal

    FOSTER CITY, Calif.  -- Scientists at Cell Genesys Inc. claimed
 major progress toward producing totally human monoclonal antibodies
 to fight disease.
    Commercially available monoclonal antibodies mimic the ones
 humans produce in that they are very specific proteins that home in
 on diseases.  However, since they are manufactured in mice, their use
 in people has been limited because the mouse proteins provoke
 allergic reactions in people.  But now Cell Genesys says it is close
 to getting around that problem.
    Cell Genesys senior scientist Aya Jakobovits and her colleagues
 have used a technology called genetic targeting to create two
 strains of mice -- one strain that is genetically purged of its
 mouse immune system, and another strain endowed with a large human
 gene.  When bred together, the offspring of such mice should produce
 purely human antibodies later this year, the company predicts.
    Reports on the work are being published this week in the British
 scientific journal Nature, and the Proceedings of the National
 Academy of Sciences.
    Genesys' executives said the company's first monoclonal
 antibodies may be made against inflammatory disease, but they added
 the approach offers promise for a number of chronic conditions such
 as arthritis, autoimmune diseases, cancer and transplant rejection.
    To create its mice, the company employs genetic targeting which
 -- unlike conventional cloning employed in standard biotechnology --
 exploits a natural form of gene-splicing known as homologous
 recombination, which the company says is simpler.
    In its mouse work, Cell Genesys also used artificial chromosomes
 derived from yeast as a carrier to introduce a very large piece of
 human DNA into mouse embryo cells.  In this case, the inserted DNA
 was simply a marker gene, carrying the blueprint for the human
 enzyme HPRT. Cell Genesys reported the HPRT gene was permanently
 installed and functioning in the mice.  The next step will be to
 insert the genes for a wide repertoire of human antibodies.
    Skeptical of any breakthrough claims, Jim McCamant, editor of the
 Medical Technology Stock Letter, said great strides toward
 humanizing antibodies already have been made by Scripps Research
 Institute in La Jolla, Calif., as well as by companies such as
 Protein Design Labs Inc., Mountain View, Calif., and Genentech Inc.,
 South San Francisco.
    "We have a slew of things going on in this field," Mr. McCamant
 said.  However most of the research has involved taking monoclonal
 antibodies made in mice and tinkering with them by attaching human
 proteins after the fact.  Universal T-Cells and AIDS Daniel Capon,
 vice president of research, acknowledged that there's intensive
 effort to "humanize" existing mouse monoclonals, but he predicted,
 "We'll make it obsolete.  We believe when the technology has been
 fully realized, the choice will be clear."
    In an editorial accompanying the Nature paper, University of Utah
 scientist Mario Capecchi praised the Cell Genesys report, along with
 research from the German Cancer Research Center in Heidelberg, as
 "an exciting new development for the molecular analysis of mammalian
 biology."  The company added its mouse model opens up new
 opportunities to study the structure and function of genes.
    In 1991, Cell Genesys teamed up with a research unit of Japan
 Tobacco Inc. to create a 50-50 joint venture called Xenotech to
 market purely human monoclonals from engineered mice.  The Japanese
 firm so far has pledged as much as $24 million in funding.
    The program also envisions the use of its targeting technology to
 produce human proteins, as well as "universal transplant cells" for
 cellular replacement therapies which will not be rejected by the
 recipient's immune system.
    The first test of the transplant cells will come later this year,
 when Cell Genesys plans to launch human trials of a "universal"
 T-cell treatment that will infuse AIDS patients with specially
 engineered white blood cells known as "killer cells" in an effort to
 attack the fatal virus.

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