GENEREX BIOTECHNOLOGY PRESENTS ADDITIONAL IMMUNOTHERAPEUTICS STUDY RESULTS AT THE 41ST ANNUAL MEETING OF THE EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES
Toronto 9/15/2005 04:30 PM GMT (WooEB)
Generex Biotechnology Corporation (NasdaqSC: GNBT), a leader in the area of buccal drug delivery, today announced further clinical trial results generated by Antigen Express, Inc., the Companys wholly-owned immunotherapeutics subsidiary.
Marta Vadacca of Universit Campus Bio-Medico, Rome, Italy presented a study titled Study of T Cell Responses to Ii-Key/MHC Class II Epitope Hybrid Peptides in Human Type 1 Diabetes.
Type 1 diabetes (T1DM) is a chronic T cell-mediated autoimmune disease that results in the destruction of the insulin-producing beta cells of the pancreas. HLA class I and class II molecules play a major role in the presentation of short pathogen-derived peptides to T cells, a process that initiates the adaptive cellular and humoral immune responses.
A novel approach to study antigen presentation by HLA Class II is based on immunoregulation by Ii protein of peptide charging to HLA class II molecules. It has been shown that a peptide of the Ii protein (Ii-Key) enhances in vitro presentation of antigenic peptides, thus creating a therapeutic opportunity to regulate the antigenic peptide binding to MHC Class II molecules. The aim of this study was to apply this technique to testing the use of Ii-Key/MHC class II insulin epitope hybrids in characterizing anti-insulin T cell responses in patients with T1DM.
Peptides of insulin shown by others to be recognized by CD4+ T cells of T1DM patients were selected from the literature. Predicted DRB1*0301 and DRB1*0401 epitopes were identified with the Rammensee SYFPEITH program (http://syfpeithi.bmi-heidelberg.com/Scripts/MHCServer.dll/EpPredict.htm) applied to the insulin peptides. Within a homologous series of hybrids with nested deletions from the N-termini of the epitope-containing segment, the longest and shortest hybrids were assayed with the shortest epitope-only peptides as controls. Five series (15 hybrids and five epitope-only controls) were analyzed. Peripheral blood mononuclear cells (PBMC) were assayed from 17 patients (9 male) mean age of 35 years (age range 15 - 58 years) affected by T1DM, with mean disease duration of 20 years (range 10 26 years), and 8 normal subjects (5 male) with mean age of 39 years (age range 15 57 years). PBMCs were cultured with PHA as positive controls and all the Ii-Key hybrids as well as epitope-only controls for both IFN gamma analysis by BD ELISPOT and T cell proliferation measured by tritiated thymidine incorporation.
Both basal IFN gamma and proliferation were normal in patients with T1DM, and there was no significant difference between patients and controls. After PHA stimulation, both IFN gamma production as well as tritiated thymidine incorporation were significantly increased in both T1DM patients and controls (p< 0.001 for all comparisons). Both patients and controls had similar responses in terms of tritiated thymidine incorporation or IFN gamma production; there was no significant difference in responses to insulin peptides either with or without Ii-Key hybrids. However, some patients had strong responses to selected peptide hybrids and others had reduced responses, suggesting heterogeneity of the response, which could have masked the nature of the response. The basis for such differences in selected patients is the subject of continuing studies.
Ii-Key/MHC class II epitope hybrids are a novel reagent to analyzing T cell responses to antigens in autoimmune disease, where often the frequency of antigen-specific precursor cells in the blood is low. The results indicate heterogeneity in the nature of the response in T1DM, whilst confirming that selected patients respond well to the Ii-Key hybrids.
Generex is engaged in the research and development of drug delivery systems and technologies. Generex has developed a proprietary platform technology for the delivery of drugs into the human body through the oral cavity (with no deposit in the lungs). The Companys proprietary liquid formulations allow drugs typically administered by injection to be absorbed into the body by the lining of the inner mouth using the Companys proprietary RapidMist device. The Companys flagship product, oral insulin (Oral-lyn), which has been approved for commercial sale in Ecuador for the treatment of patients with Type-1 and Type-2 diabetes, is in various stages of clinical trials around the world. Antigen Express is a wholly owned subsidiary of Generex. The core platform technologies of Antigen Express comprise immunotherapeutics for the treatment of malignant, infectious, allergic, and autoimmune diseases.
For more information, visit the Generex website at www.generex.com and the Antigen Express website at www.antigenexpress.com.
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