PR Newswire; Tuesday December 23, 8:29 am EST

"Although numerous peptides able to induce an immune response in vitro have been identified, they have been difficult to develop as therapeutic agents because they are weak antigens in vivo, and therefore, would require extremely large dosages to produce a clinically-meaningful effect," said Ben Bronstein, M.D., President and CEO of Peptimmune, Inc. "Studies conducted by Drs. Kirsten Falk and Olaf Rotzschke, in the laboratory of Dr. Jack Strominger, and reported in PNAS, show that specific peptide oligomers are able to generate up to 10,000-fold increases in potency over non-linked peptide antigens or whole protein antigens. This suggests that Peptimers(TM), proprietary peptide oligomers under development by Peptimmune, could serve as clinically-beneficial agents at significantly lower dosages than peptides."

Peptimmune, Inc., the exclusive licensee of this technology from Harvard University, is applying Peptimer(TM) technology to the discovery and development of therapeutics to treat autoimmune and viral diseases. Dr. Bronstein noted that the Peptimer(TM) technology is one of three complementary platforms that the Company is developing based on fundamental discoveries by its scientific founders in the area of antigen processing and presentation, the "headwaters" of the immune response. These platforms are designed to yield highly specific treatments that target the underlying mechanism of the disease process, without producing the adverse effects resulting from general immunosuppression.

In the studies reported in PNAS, the researchers produced peptide oligomers derived from an influenza virus protein antigen. They then compared the ability of peptide oligomers, non-linked peptides ("peptide monomers") and whole protein antigens to generate immune responses as measured by the expression of key cell surface molecules and the proliferation of T cells in vitro. The results indicate that the Peptimers generate immune responses similar to those of peptide monomers and whole protein antigens at concentrations up to 10,000 times lower than the corresponding peptide monomer or whole protein antigen.

While the mechanism underlying this heightened response to peptide oligomers is not known, immune responses to peptide antigens are triggered when receptors on T cells bind the MHC molecule/peptide antigen complexes on the surface of antigen presenting cells. Additional studies suggest that clustering of the resulting MHC molecule/peptide antigen/T cell receptor complexes is critical to T cell activation and the subsequent immune response. Peptide oligomers were designed to induce and amplify cell surface clustering of these receptor complexes.

Additionally, the authors have found that as the amount of peptide oligomer used in in vitro is increased, a leveling off of T cell proliferation occurs. These findings suggest that at dosages many fold lower than corresponding dosages of peptide monomers, peptide oligomers could serve as potent and specific suppressors of harmful immune responses, e.g. autoimmune diseases.

This approach to the treatment of autoimmune diseases is based on an extensive body of research, which demonstrates that large doses of a peptide antigen paradoxically can induce immune system "tolerance" to that antigen, rather than immune system activation. Based on these published reports and other scientific studies performed in Dr. Strominger's laboratory, the Company has begun to develop Peptimers for the treatment of several types of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis.

Additionally, the Company plans to develop Peptimers as immune system "superactivators" for use as therapeutic vaccines against viral infections. HIV infection will be the first viral disease to be addressed. The Company's HIV program is based on the discoveries of Bruce Walker, M.D., Director of the Partners AIDS Research Center at the Massachusetts General Hospital and his colleagues, who recently identified novel HIV peptides that stimulated helper T cells from the blood of certain long-term survivors infected with HIV (reported in the November 21, 1997, edition of Science). The Company plans to conduct studies in collaboration with Dr. Walker and his colleagues using Peptimers containing selected HIV peptides.

The paper is entitled "Superactivation of an Immune Response Triggered by Oligomerized T Cell Epitopes." In addition to Dr. Strominger, Higgens Professor of Biochemistry at Harvard University and the Dana Farber Cancer Insititute, the article's lead authors are Kirsten Falk, Ph.D., and Olaf Rotzschke, Ph.D., both researchers in Dr. Strominger's laboratory at Harvard University.

Peptimmune discovers and develops therapeutics for immune system regulation based on an advanced understanding of antigen processing and presentation, the initiating events of the immune response. The Company's initial development efforts are in the areas of autoimmune and viral diseases.

SOURCE: Peptimmune, Inc.

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