Genentech Inc. has constructed "humanized" versions of itsmouse antibodies for treating cancers, and one of theantibodies has shown the same potency as a previous mouseversion in stopping cancer growth in lab cultures.

As published in the May 15 Proceedings of the NationalAcademy of Sciences, a monoclonal antibody (MAb) combiningelements of the mouse antibody with human antibody proteinwas even more efficient in prompting the killing of certaincancer cells by immune system cells.

Humanized antibodies take the targeting end of the mouseimmunoprotein and splice it to a human antibody. The aim is tomake the chimeric molecule less likely to provoke an immunereaction.

The South San Francisco, Calif., company (NYSE:GNE) has startedtesting its mouse version in Phase I trials in patients withbreast and ovarian cancers. The second-generation, humanizedMAb is scheduled to enter the clinic sometime in this year, saidspokesman Jim Weiss.

Genentech's anti-cancer MAbs are targeted against the HER-2protein, which causes a particularly virulent form of cancerthat responds poorly to traditional therapies. The MAb binds toa receptor on the protein, preventing it from causing theunchecked growth of tumor cells.

Healthy people have a single copy of the HER-2 oncogene,which produces HER-2 protein. But about one-third of cancerpatients have between 20 and 40 extra copies of the gene.These patients produce 50 to 100 times the normal amount ofHER-2 protein, resulting in an aggressive form of cancer.

Genentech is also collaborating with NeoRx Corp.(NASDAQ:NERX) on the HER-2 monoclonal, with the antibodyserving as a carrier for NeoRx's radiotherapy. Genentech hastested the mouse antibody with an iodine radiolabel in Phase Itrials. In February, NeoRx signed a second collaboration to testthe antibody-guided radiotherapy in a preclinical programusing the Seattle company's rhenium labeling technologies withGenentech's humanized version.

-- Roberta Friedman, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.