When a cancer begins to form in the body, the body'simmune defenses don't take the growing threat lyingdown. That police force of antibodies and killer cellslooks just as askance at malignancies as it does atpathogenic viruses, bacteria and bee stings.

Most often _ according to the doctrine of immunesurveillance _ the patrolling immunity enforcersterminate the incipient tumor before it gets much past cellone. Unhappily, as in other forms of crime prevention, atleast a million times a year in the U.S. alone, theburgeoning mass of malignant cells outsmarts oroverpowers those immune defenders, and goes on to killthe patient.

Decades of war-on-cancer research have so far merelymade the statistical rubble of cancer mortality bounce.But scientists' expanding knowledge base of what makesmalignancies happen and metastasize is beginning tomake oncologists more optimistic.

One of the most optimistic issurgeon/immunologist/molecular oncologist StevenRosenberg, who heads the National Cancer Institute's(NCI) surgery branch. One of Rosenberg's latest andbrightest reasons for optimism is a highly specializedkiller T cell of the immune system's cellular arm.

These tumor-infiltrating lymphocytes (TIL) smugglethemselves into specifically targeted solid tumors, andfinish them off. At least, that's their mission. In practice,TILs are all too often too few or too weak to finish thejob.

Rosenberg has invented a process that greatly expands apatient's home-grown TIL cells, and energizes them todestroy the tumor. It involves incubating them for severalweeks in the presence of interleukin-2 (IL-2). This is apotent cytokine, itself secreted mainly by helper T cells,which causes other T cells, such as the likes of TIL, toproliferate and go into action.

A government patent, number 5,126,132, dated June 30,1992, and titled "Tumor infiltrating lymphocytes as atreatment modality for human cancer," protectsRosenberg's invention. Now the National Institutes ofHealth (NIH) proposes licensing it in exclusivity toApplied Immune Sciences Inc. (AIS) of Santa Clara,Calif. Last week, NIH's Office of Technology Transferforwarded an announcement of this intent to the FederalRegister.

"TIL cells," Rosenberg told BioWorld Today, "representthe best available way to recognize tumor antigens; toidentify specific immune reactivities in cancer patients."

He added, "We've used them in the past year to actuallyclone the genes that code to six different cancerantigens."

At present, NCI's surgery branch is using TILs to treatpatients with advanced melanoma, and "sees responses in35 to 40 percent," Rosenberg said. Of the first 263 TILpatients, 7 percent shed their tumors completely; 10percent, partially.

A few other non-commercial centers also have limited,experimental TIL therapy programs. The approach is notyet FDA-approved.

"The whole issue now," Rosenberg observed, is: "Canthis therapy be made more widely available? Not just formelanoma, but to treat other diseases." He concluded, "Iguess that's what AIS wants to do."

"We have definite plans to extend the TIL therapy toother cancers besides melanoma," said Jane Lebkowski,the company's vice-president of research anddevelopment. She added, "Particularly metastatic solidtumors, such as lung, colon and renal-cell carcinomas."

AIS already has a Phase III randomized, clinical trialgoing of TIL-based treatment for renal-cell carcinoma.(See BioWorld Today, Dec. 16, 1994, p. 3.) The companyis building cell therapy centers in the U.S., Europe andJapan, Lebkowski said, to process the tumor tissues takenfrom patients.

Two already are operational in California, a third is underconstruction at Duke University.

"These centers look like bank upon bank of incubators,"AIS patent attorney Ken Moseley told BioWorld Today."When a patient's tumor is flown into the center," hesaid, "it's minced, digested, and put in long-term cultureof TIL cells. We then fly these back out to the patient fortreatment."

So, Moseley explained, "it's become time for us to lookat the patent situation, and try to close off any loose ends.Of course the Rosenberg patent was out there; whether itcovers our process or not is an open question. You neverknow in patents these days what a claim covers or doesn'tcover.

"But," he added, "we probably thought it made goodbusiness sense to attempt to get an exclusive, royalty-bearing license to it. As far as we know, we at AIS are theonly ones who have done so." n

-- David N. Leff Science Editor

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