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BioTransplant Announces Advances in Cell Therapy

BioTransplant Incorporated (Nasdaq: BTRN) today reported important advances towards solving the problem of rejection of foreign proteins in transplantation. Using enhanced green fluorescent protein (EGFP) as a model antigenic protein, BioTransplant researchers have established a pre-clinical model of immune tolerance for cellular transplants. The data will be presented at the 43rd Annual Meeting of the American Society for Hematology (ASH) in Orlando, Florida.

EGFP is commonly used as a “reporter protein” in gene transfer protocols because it produces a green color and can be seen in cells. When it is linked to a medically important gene, it “reports” that the gene has been successfully delivered to the host cell. However, an immune response against EGFP itself frequently occurs. To determine if tolerance could be induced against the foreign protein, mice were treated with a proprietary regimen including bone marrow cells that express the foreign gene product. This protocol re-educated the recipient’s immune system to accept EGFP as “self.” When the mice were later given skin grafts from donor mice with the EGFP gene, the grafts were accepted and maintained. In contrast, skin grafts transplanted on control mice were rejected.

In addition to these pre-clinical results, significant clinical data will be presented. In separate studies, Dr. Jerome Ritz, Director of the Connell O’Reilly Cell Manipulation and Gene Transfer Laboratory at Dana-Farber Cancer Institute, demonstrated the value of depleting CD8+ T cells from a donor lymphocyte infusion (DLI) to reduce graft-vs-host disease (GvHD). Donor lymphocyte infusions are often given after bone marrow transplants in order to provide additional immune competent cells, hasten immune reconstitution and provide additional anti-tumor activity. Frequently, however, DLIs are associated with GvHD. In a clinical trial including patients with AML, MDS, ALL, CLL, NHL and myelofibrosis, patients were randomized to receive either unselected DLI or CD8-depleted at 5-7 months post bone marrow transplant. Patients in both groups received identical numbers of CD4+ T cells. Nine patients received CD8-depleted DLI and did not develop GvHD. In contrast, six of nine patients who received non-depleted DLI subsequently developed significant acute GvHD. The estimated two-year relapse-free survival post BMT was 86% in the patients receiving CD8-depleted DLI, compared with 52% of patients receiving unselected DLI.

“Clinical and laboratory studies such as the ones we are reporting at the ASH meeting in Orlando suggest that depletion of the CD8+ cells from the DLI reduces the risk of GvHD following treatment,” said Dr. Ritz, who is a consultant to BioTransplant. “Despite reducing GvHD, the CD8-depleted DLI continues to induce an anti-tumor effect and also has other positive effects on immune function.”

BioTransplant’s Eligix(TM) Cell Separation System technology is a family of proprietary cellular therapeutic products, which are designed to have broad applications for treating certain blood cancers and solid tumor cancers, as well as autoimmune diseases and other conditions. The System specifically addresses treatment of blood cancers by eliminating T cell subsets via High Density Microparticles (HDM) which are coated with the antibody specific for the cell population to be removed. The cell separation system is expected to enhance allogeneic transplant procedures by reducing the risks of relapse and GvHD, while maintaining an anti-leukemia effect.

“GvHD is a serious complication of transplantation biology,” said Elliot Lebowitz, CEO of BioTransplant. “These results are exciting and support the necessity for eliminating T cell subsets from Donor Lymphocyte Infusions. BioTransplant’s system will potentially decrease the occurrence of GvHD without compromising the anti-tumor activity.”

The same investigators will also present data on the immunologic effects of DLI and the mechanism responsible for this phenomenon. Patients with relapsed CML who receive CD8-depleted DLI are able to achieve complete cytogenetic and molecular remission. The cells responsible for this effect appear to recognize minor histocompatibility antigens. Despite the removal of CD8+ cells from the DLI, studies show that this treatment induces the expansion of CD8+ effector T cells specific for minor histocompatibity antigens in vivo. Together, these papers provide a significant rationale for CD8-depletion of DLIs.

BioTransplant Incorporated utilizes its proprietary technologies to re-educate the body’s immune responses to allow tolerance of foreign cells, tissues and organs. Based on this technology, the Company is developing a portfolio of products for application in a range of medical conditions, including organ and tissue transplantation, and treatment of cancer and autoimmune diseases, for which current therapies are inadequate. BioTransplant’s products under development are intended to induce long-term functional transplantation tolerance in humans, increase the therapeutic benefit of bone marrow transplants, and reduce or eliminate the need for lifelong immunosuppressive therapy. This release and additional information on BioTransplant is available on the Web at http://www.biotransplant.com.