By David N. LeffScience Editor

Immunologist Jeffrey Schlom is looking for a few good biotech firmsto cash in on the next generation of diagnostic and therapeuticmonoclonal antibodies. Schlom heads the National Cancer Institute'sLaboratory of Tumor Immunology and Biology (LTIB) in Bethesda,Md.

On the cusp of this latest "quantum leap," as he calls it, is "a hand-held Geiger counter, the size of a pen. In the hand of an oncologicalsurgeon, it looks for radioactive antibody bound to occult disease inthe open operative field."

This intraoperative radioimmunoguided surgical probe is the subjectof four Phase III clinical trials now nearly completed at 25 cancercenters in the U.S. plus another five recently added in Europe.Neoprobe Corp., of Dublin, Ohio, is conducting these pivotal studiesto test the ability of a second-generation LTIB monoclonal antibodyto localize in colorectal, breast and ovarian tumors. (See BioWorldToday, March 27, 1995, p. 1.)

"We call the prototype of these new antibodies CC49," Schlom toldBioWorld Today. "It reacts with the same tumor-associatedglycoprotein antigen, TAG-72, as its first-generation predecessor,B72.3, but binds to a different epitope of that pancarcinoma antigen,and with much higher affinity."

B72.3, he pointed out, "is the antibody in [Princeton, N.J.-based]Cytogen Corp.'s Onco-Scint agent for diagnostic imaging of colonand ovarian cancer. It is the first, and still the only, antibodyapproved by the Food and Drug Administration for any in vivo use incancer."

Schlom and his group produced B72.3 in 1979. "We did everythingright," he observed, "with no major stupidity involved, but it took 13years from the time we made that tumor-targeting antibody to itsFDA approval, just over a year ago."

Neoprobe and the NCI are in the final stages of negotiating aCooperative Research and Development Agreement (CRADA) forLTIB's CC49 antibody, the company's spokesperson, Judy Barnes,told BioWorld. Schlom observed that this pending CRADA isessentially a done deal, unlike those future ones announced by LTIBon April 25 in the Federal Register.

"Because the CC49 has performed so well in that surgical probe,"Schlom said, "it led me to believe that this new antibody may havesome important therapeutic applications." Accordingly, Phase IIclinical trials sponsored by the NCI itself, are in progress, to test theprowess of radiolabelled CC49 in killing prostatic, pancreatic,ovarian and mammary carcinoma cells.

The monoclonals, tagged with cell-zapping isotopes of iodine,yttrium or lutetium, find and bind the tumor-associated antigens.

Schlom explained that "at this moment all these trials are being donewith a mouse monoclonal antibody. This limits treatment to a singleinjection, to avoid an immune reaction. One wouldn't really expectmuch," he added, "from just a one-shot dose."

Even so, he said, "We're at the brink where we are starting to seesome objective therapeutic responses for the first time in the Phase IIprostate, breast and ovarian cancer trials. Though not dramatic, theyare clearly objective, antitumor responses."

Wanted: CRADA Collaborators With Scale-Up Savvy

Schlom continued, "We have developed humanized forms of CC49,on all kinds of genetically engineered variations, but what we'relooking for now is a CRADA partner to produce them. One withexpertise as well in drug and toxin conjugation, plus chelateconjugation. That's where our major needs are. We can do a lot ofsophisticated molecular biology and a lot of animal models, but whenit comes to making a GMP [good manufacturing practice] productand testing it, that's the purpose of a CRADA."

Editor's Note: For information concerning this CRADA opportunity,consult Michael Christini or Mark Noel, NCI Office of TechnologyDevelopment, (301) 496-0477; for technical questions concerningthis monoclonal antibody technology, Jeffrey Schlom, LTIP, (301)496-4343. [N.B. CRADA proposals must reach NCI's Office ofTechnology Development by 5:00 p.m., June 26, 1995.] n

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