Theratechnologies Inc T.TH

Great NEWS again! (from Celmed)

[joe9999]

I post this news. I like it a lot. Very very promising I think! Theratechnologies Inc. - Photodynamic Cell Therapy Viewed as the "Magic Bullet" in the Prevention of Graft-Versus-Host Disease An important study on the selective depletion of donor alloantigen-specific T-cells is featured in the scientific journal Blood MONTREAL, April 23 /CNW/ - Collaborators of Celmed BioSciences, a Montreal-based cell therapy company and subsidiary of Theratechnologies, have published groundbreaking results in the May 1, 2002 issue of Blood (Vol. 99, number 9), the prestigious journal of the American Society of Hematology (ASH). The article is featured as a Plenary paper and is commented on favorably in that same issue by Dr. Claudio Anasetti, from the Division of Clinical Research at the Fred Hutchinson Cancer Research Center. The study suggests that a photodynamic cell therapy process (PDT) can selectively deplete host alloantigen-specific T-cells to prevent graft-versus-host disease (GvHD), while preserving immune and antileukemia functions. The research was conducted by researchers from the Bone Marrow Transplantation Program at Duke University Medical Center in Durham, North Carolina. Nelson J. Chao, M.D., the director of the Bone Marrow Transplant Research Laboratory and principal investigator, conducted his work with Benny J. Chen, M.D. Dr. Chao's team is supported by a research grant from Celmed BioSciences Inc. Chen, Chao and colleagues have demonstrated in a mouse animal model that treating allogenic transplants with a photodynamic purging process using the photosensitizer TH 9402, a rhodamine-derivative developed at Celmed, selectively eliminated T-cells associated with graft-versus-host disease. GvHD is an extremely severe and frequent reaction associated with allogenic bone marrow transplants, i.e. grafts from non-compatible donors. "Selective depletion by photodynamic purging may represent a step forward in the prevention of GvHD in humans," wrote Dr. Anasetti in his commentary. The commentator enthusiastically described the approach as the potential "magic bullet" in future GvHD research. "If the biology of these findings can be extended to human cells, this approach will deserve consideration for testing in clinical trials," added Dr. Anasetti. Allogenic bone marrow transplantation-which requires external donors-has long been recognized as a treatment for patients suffering from leukemia or certain hematopoietic malignancy diseases. Since chemotherapy and/or radiotherapy completely eliminates dividing cells, the bone marrow often needs to be replaced via a graft. The patient can receive a bone marrow transplant either from a compatible or a non-compatible donor. While techniques have been developed to reduce the incidence of GvHD in patients receiving a transplant from a non-compatible donor, the mortality remains high. If the transplant is entirely depleted of its T-cells, recipients become highly vulnerable to opportunistic infections and their cancers often relapse. The difficulty is to remove specific T-cells (the cytotoxic T-lymphocytes), which are responsible for GvHD, while sparing tumor antigen-specific T-cells, which mediate the beneficial graft-versus-leukemia (GVL) effect. STUDY METHODS AND RESULTS Photodynamic cell therapy can be used to perform selective T-cell depletion. To separate host-reactive T-cells, the lymphocytes that are causing GvHD, from tumor-specific or third-party-specific T-cells, researchers have put these cells in contact with the spleen cells of host mice. Cytotoxic T- lymphocytes are thus activated, while all other T-cells remain at rest. The photosensitizer TH 9402 is then added to the culture flasks. This molecule is selectively retained inside the mitochondria of activated host-reactive T- cells. When TH 9402 is exposed to visible light from a scanning lamp device (Theralux(TM)), an oxidation process takes places and cell death ensues. The photodynamic cell therapy process inhibited cytotoxic T-lymphocytes by 93% and reduced the production of interferon-y by 66%. Bone marrow transplants depleted from host-reactive T-cells were tested on mice in vivo. Grafts were performed by intravenous injections in the rodents' tail. In a first group of mice inoculated with a leukemia-causing cell line before transplant, all animals developed leukemia within 30 days, with a 50% mortality rate at 100 days. When these mice received a transplant of untreated cells, they all died of GvHD. The clinical signs of GvHD (weight loss, hair loss, erythema) were monitored daily. However, in another group of mice, the addition of PDT-treated cells led to a 90% survival rate at 100 days. No sign of GvHD and no tumors were detected. The study shows that a graft previously treated ex vivo with TH 9402 does not induce GvHD and is well tolerated by the recipient. The GVL effect is strongly preserved, which allows the graft to inhibit residual cancer cells and leukemia relapses. Moreover, transplants have been shown to retain their ability to induce GvHD in third-party mice. Since only specific T-cells are purged, the immune function is not suppressed and recipients are able to fight infections. THERAPEUTIC APPLICATIONS PDT-treated T-cells can potentially be used in novel therapies. They can be given to human patients together with hematopoietic stem cells, or be used as a T-cell source for delayed lymphocyte infusions. For PDT therapy to be efficient, T-cells need to be activated exclusively by host histocompatibility antigens, without activation of tumor antigens. If this was so, useful T-cells would be lost in the purging process. While this is easily attainable with inbred mice, it may prove to be more difficult on humans suffering from cancer. Celmed is currently exploring solutions to avoid this problem and will conduct more studies to this effect. A considerable advantage of the TH 9402 treatment is that it rests on visible light at a specific wavelength (514 nm). A patient's bone marrow cells are thus never exposed to UV radiations. Since the transplant is treated ex vivo (outside the body), a patient would be assured to receive only a healthy graft, with no risk of rejection. "The potential applications of this innovative treatment are many. We intend to initiate clinical trials in the coming months for the GvHD indication to verify the efficacy of our photodynamic treatment in human subjects," said Dr. Luc Villeneuve, Ph.D., Chief Scientific Officer at Celmed BioSciences. CELMED BIOSCIENCES Celmed BioSciences is a new subsidiary created by Theratechnologies in June 2001 in order to maximize the significant potential offered by its cell therapy activities. With facilities in Canada and the US, Celmed is dedicated to the treatment of neurological, hematological and immunological disorders using adult stem cell technologies. By integrating personalized medicine and basic molecular biology tools revealing each individual genomics and proteomics profile, Celmed dedicates its efforts to develop new biological selective therapies. Celmed BioSciences' website is located at www.celmedbio.com. THERATECHNOLOGIES A leader in the biopharmaceutical field in Canada, Theratechnologies has developed an innovative therapeutic platform offering numerous applications in the field of therapeutic peptides targeting endocrine and metabolic disorders. In light of promising clinical results and the commercial potential of its lead peptide, ThGRF, Theratechnologies has implemented an aggressive strategy, consisting of pursuing several indications addressing largely unmet clinical needs, using novel delivery systems. Theratechnologies' website is located at www.theratech.com. The Company is listed on the Toronto Stock Exchange under the symbol TH. For further information: Patricia Delaney Lussier, Communications Director, Theratechnologies, [phone], ext. 234, [e-mail]