Apoptosis Technology Inc. (ATI) and the Imperial Cancer ResearchFund (ICRF) of London said Monday they will collaborate onresearching the process of cell proliferation and apoptosis, orprogrammed cell death.ATI, a subsidiary of ImmunoGen Inc. that focuses on the company'sapoptosis program, will make undisclosed research payments to ICRFfor three years, and pay royalties on any future product sales. ICRFalso received 3 percent equity in ATI, Mark Ratner, ImmunoGen'sexternal communications director, told BioWorld.ATI, of Cambridge, Mass., gets access to work being done by GerardEvan and Hartmut Land at ICRF, including the use of proprietaryscreening systems for identification of compounds involved inregulation of cell proliferation or apoptosis."It would take ATI years to develop these screens independently," saidMitchel Sayare, ATI's president and the chairman and CEO ofImmunoGen. "We also have access to ICRF's substantial body ofknowledge about mechanisms of cell growth and apoptosis as theyrelate to cancer and the growth of tumors. Among other things, weexpect [the collaboration] to lead to the development of products whichtrigger apoptosis in cancer cells."Evan and Land have been looking at the myc gene and at insulin-likegrowth factor-1 (IGF-1), both of which have been observed tomodulate apoptosis and cell proliferation, Ratner said.Evan has been studying the regulation of cell death pathways bysurvival signals, such as IGF-1."We have shown that survival signals provided by IGF-1 help preventmyc-transformed tumor cells from undergoing apoptosis," Evan said ina news release. "One goal of this collaboration, therefore, is to dissectthe role of IGF-1 and other survival factors in the death pathway and touse molecular screening to identify drugs that mimic or disrupt thesurvival signal of IGF-1 in cells. We expect that down-regulation ofsurvival signals will induce apoptosis in a great number of tumors."Land's focus has included studying the regulation of cell proliferationsignals."Inappropriate expression of the myc gene product is implicated in theabnormal cellular proliferation seen in tumors," said Walter Blattler,ImmunoGen's vice president of research. "Myc only can act inconjunction with its normal cellular partner, Max. Working with Land,we expect to identify agents that interfere with the Myc/Maxheterodimer, thereby contributing to the inhibition of cellproliferation."ATI was formed in January 1993 to hold rights to products thatresulted from the Boston-based Dana-Farber Cancer Institute'sapoptosis work. ATI also is working with St. Louis University MedicalCenter and the Fred Hutchinson Cancer Research Center in Seattle onbcl-2 and related genes as regulators of apoptosis."ImmunoGen views this investment [ATI] as its long-term focus whichwe think will add to our product pipeline in five to 10 years," Ratnersaid. "ATI will look at the screening systems that it's working withnow and make some hard decisions on diseases and product candidatesin the next six to 12 months."The company's lead platform technology involves its Oncolysinproducts, which are conjugates of monoclonal antibodies to blockedricin, a potent plant toxin. Four products are in clinical trials, includingthe lead product, Oncolysin B, which is in a pivotal Phase III trial fortreatment of lymphoma. ImmunoGen's second technology area is insmall-molecule drugs for cancer. The company filed its firstinvestigational new drug application in that area in April, and hopes tostart a clinical study this fall of B4-DC1 for lymphoma.ImmunoGen stock (NASDAQ:IMGN) closed at $3.75 per shareMonday, down 50 cents. n

-- Jim Shrine

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