A promising potential anti-cancer agent makes tumors inresearch animals disappear completely, studies by the NationalCancer Institute (NCI) showed.

This week's edition of the journal Cancer Research features anarticle on this agent, based on a monoclonal antibodydeveloped by Immunomedics Inc. of Morris Plains, N.J.

Linked to a toxin derived from Pseudomonas bacteria, theantibody reduces tumors by 80 percent in laboratory animalswith B-cell non-Hodgkin's lymphoma. A fragment of theantibody, called Fab, destroyed all the tumor cells.

Fab seems to penetrate better because it is smaller, explainedHans Hansen, principal investigator of the study and vicepresident of exploratory research at Immunomedics(NASDAQ:IMMU). Also, the toxin is located away from the partthat binds the tumor cell.

The agent "is internalized very rapidly into the cell," Hansensaid. "It is probably as effective as any other toxin antibodyhas been shown in preclinical studies to target and kill cells."

Immunomedics has begun Phase I clinical trials in patientswith B-cell non-Hodgkin's lymphomas of its whole antibody,LL2, linked to the radioisotope I-131. This high-energy isotopekills cells in its vicinity with a so-called "bystander" effect.

"Once you have an antibody that will internalize so easily,"Hansen said," there are a number of different options to allowyou to develop better therapeutics."

Fab could be linked to drugs or low-energy radioisotopes thatonly kill cells from inside or when attached to the membrane.Treatment with a low-energy isotope would be useful whentumors have invaded bone marrow, for instance, savingplatelets and granulocytes from damage so they can preventinternal bleeding and engulf germs.

"There's a place for both an isotope that will kill a significanttumor mass and one that will mop up," Hansen said.

The NCI has a leading program in investigation low-levelradioisotopes as cancer treatments. Meanwhile, ImmunoGenInc., Xoma Corp. and Seragen Inc. have worked on targetingtoxins to tissues with antibodies.

-- Nancy Garcia Associate Editor

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