The July edition of the Journal of Immunology, a peer-reviewed research publication of the American Association of Immunologists, features an article that will detail the research collaboration between Generex's (GNBT) wholly owned subsidiary, Antigen Express, and the Mayo Clinic. The research is a continuation of scientific study between Antigen Express, lead by President Dr. Eric von Hofe, and the Mayo Clinic's Dr. Keith Knutson, a leader in the field of peptide vaccines in breast cancer. The title of the future article is "MHC Class II Epitope Nesting Modulates Dendritic Cell Function and Improves Generation of Antigen-Specific CD4 Helper T Cells". The abstract and article are not yet available for view, but the title is included in the Journal's future table of contents.
Antigen Express has been developing a series of CD4+ T Cell helper epitopes, based upon their proprietary Ii-Key hybrid technology. Ii-Key is a portion of the MHC class II associated invariant chain, which is known as Ii. Antigen Express explains that Ii-Key facilitates the direct loading of epitopes to the MHC class II molecule groove. Utilizing their technology, Antigen Express' Ii-Key/MHC class II epitope hybrids have shown clinical evidence of greatly enhancing the vaccine potency of the tethered epitope. Antigen Express' most advanced vaccine is AE37, a HER-2/neu hybrid peptide which is currently in a multi-center Phase II study.
The Mayo Clinic's Dr. Knutson has long studied adoptive T Cell therapy strategies to create cancer vaccines designed for immunotherapy of HER-2/neu breast cancer. Adoptive T Cell therapy strategies have largely focused generation of CD8+ T Cells, due to observations that most tumours express MHC class I, but not MHC class II. This gets tricky, so here is some info on CD4+ T Cells vs CD8+ T Cells. CD4+ T Cells recognize antigen-derived peptides in the context of self-MHC class II molecules, while CD8+ T Cells recognize antigen derived peptides in the context of self MHC class I molecules.
The problem Dr. Knutson had previously encountered is that CD8+ T-cells have a short lifespan. Earlier, Dr. Knutson reported that a problem with the use of adoptive T Cell therapy included the lack of CD4+ T cell help. In further work, Dr. Knutson has found that patients immunised with with CD4+ HER-2/neu helper epitopes, such as being developed by Antigen Express, are able to develop long lasting HER-2/neu specific CD8+ T Cell immunity. Specifically, Dr. Knutson found that greater than 60% of patients immunised with CD4+ HER-2/neu helper epitopes, each containing an encompassed HLA-A2 epitope, were able to develop HER-2/neu specific CD8+ T-cell immunity. The CD8+ T Cell response was maintained, in some patients, for at least one year following vaccination.
In contrast, 40% patients immunised with a single CD8+ T Cell HER-2/neu HLA-A2 9-merpeptide, RXI Pharmaceuticals' (RXII) NeuVax, or E75, developed HER-2/neu CD8 T Cell immunity that declined to undetectable levels within 5 months of the last vaccination. AE37 is the HER-2/neu CD4+ T Cell helper containing an encompassed HLA-A2 epitope that outshines E75 given alone in his study. If a main problem for Dr. Knuston's adoptive transfer research had been the lack of CD4+ T cell help, Dr. von Hofe and Antigen Express presented the solution.
Since we know the title of the upcoming research article authored by Dr. Knutson and Dr. von Hofe, with other Mayo Clinic researchers, is "MHC Class II Epitope Nesting Modulates Dendritic Cell Function and Improves Generation of Antigen-Specific CD4 Helper T Cells", we have a clue on where they are going with this research. A 2010 patent by Dr. Knutson, titled "METHODS AND MATERIALS FOR GENERATING T CELLS", explains what is invloved in generating antigen-specific CD4+ T cells. The patent outlines methods and materials for using nested MHC class II epitopes to generate CD4+ T cells. The patent states that the nested MHC class II epitopes provided can include an invariant chain, or Ii, and a MHC class II epitope. The patent is describing his work with Antigen Express, and the upcoming article will provide peer review documentation.
Antigen Express is also involved in a separate collaboration with the Mayo Clinic's Dr. Svetomir Markovic, a distinguished translational researcher with expertise in melanoma trials. That agreement focuses on advancing an immunotherapeutic vaccine for melanoma into the clinic. Generex is planning a spin out of Antigen Express, following approval of a reverse stock split of Generex's shares. Top industry scientists, like those found at the prestigious Mayo Clinic, are already excited about the potential found within Antigen Express' pipeline. I am certainly no scientist, so read my opinions and rough analysis with that in mind, but the potential for Antigen Express is obviously high.
Should Generex's planned reverse stock split proposal be approved, followed by a spin out of Antigen Express, adequate funding may finally be within Antigen Express' grasp, which will serve as the fuel to propel all of this successful research deeper into human studies. The winners in that scenario will be Generex's current and Antigen Express' future shareholders, and most importantly the cancer patients in need of better therapy. We are looking at the future when active immunotherapy will be a commercialized reality, designed by Antigen Express.
Showing posts with label Ii-Key. Show all posts
Showing posts with label Ii-Key. Show all posts
Wednesday, May 25, 2011
Thursday, November 25, 2010
Generex's Antigen Express and France's Stallergenes Co-Author Allergen Research
Scientists from Antigen Express, a wholly owned subsidiary of Generex Biotechnology (GNBT), and France's Stallergenes (GENP.PA) have co-authored a peer review article titled "Researchers Distinct Characteristics of Seasonal Bet v 1 vs. Perennial Der p 1/Der p 2 Allergen-Specific CD4+ T Cell Responses". The article will appear in a future edition of "Clinical & Experimental Allergy" and is available online ahead of print as of November 24th. Stallergenes is a biopharmaceutical company dedicated to immunotherapy treatments for the prevention and treatment of allergy-related respiratory diseases, such as allergic rhinoconjunctivitis, rhinitis and asthma.
Stallergenes has been researching the potential of using Ii-Key peptide tetramers as an assay to monitor T cell responses to allergens as part of a collaboration with Antigen Express that was signed in 2005. Since Antigen Express' proprietary Ii-Key peptide hybrids are potent at stimulating CD4+ T cells, in theory they would be useful in detecting the presence of allergen-specific autoimmune T cells in the blood. The CD4+ T cell responses to the Ii-Key assay will evidently help Stallergenes identify which patients would benefit from the specific immunotherapies which they are developing.
The new research article compares the CD4+ T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens. Bet v 1 refers to birch pollen allergen while Der p 1, Der p 2 are considered to be the major allergens derived from house dust mites. The researchers inform that "major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses". A little cheating from Wikipedia tells us that "histocompatibility is the property of having the same, or mostly the same, alleles of a set of genes called the major histocompatibility complex. These genes are expressed in most tissues as antigens, to which the immune system makes antibodies".
The new report from Antigen Express and Stallergenes states that "tetramer+ cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non-allergics". The report concludes that "different memory CD4+ T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4+ T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy".
A previous peer review published in 2008 by Antigen Express and Stallergenes, titled "Single Cell Assessment of Allergen-Specific T Cell Responses with MHC Class II Peptide Tetramers", revealed that the complex class II peptide tetramers, such as those mentioned in in the new report, were peptides that are "chemically conjugated with the Ii-Key peptide from the MHC invariant chain to facilitate peptide exchange and binding to MHC class II molecules". In the report, the researchers described that the CD4+ T helper cells that are activated to respond to specific allergens can be identified with high sensitivity ex vivo using Ii-Key hybrids. The researchers of the article remarked that Ii-Key peptide tetramers "will also be extremely useful to monitor the efficacy of various immunotherapeutic strategies in humans, using an immunological readout, possibly helping to identify surrogate biological markers of clinical efficacy" and that "Ii-Key conjugate peptides is the most efficient procedure to expand Bet v 1(141-155)-specific CD4+ T cells, allowing to detect such cells in both allergic and healthy individuals".
In April, Stallergenes announced the positive results of a phase III clinical trial conducted in the US for its sublingual grass pollen immunotherapy tablet, Oralair. The Phase III study is the first conducted in the US, after successfully completing four Phase III clinical trials conducted in Europe. Oralair has already been approved by German regulators, and Stallergenes has retained Torreya Partners in hopes of helping them secure a partner for the US market by mid-2011. Stallergenes is currently planning their NDA filing to be submitted to the FDA.
Stallergenes is aware that they also need help in evaluating which patients would most benefit from their allergen immunotherapy tablets, and in their scientific research reports we find evidence that this help may come from an Antigen Express designed assay. Antigen Express' ability to turn their Ii-Key peptide tetramer assay research into a revenue generating asset may not be such a far fetched dream. While that dream remains to be seen, this positive research report concerning Antigen Express' proprietary Ii-Key technology is certainly a step in the right direction.
Stallergenes has been researching the potential of using Ii-Key peptide tetramers as an assay to monitor T cell responses to allergens as part of a collaboration with Antigen Express that was signed in 2005. Since Antigen Express' proprietary Ii-Key peptide hybrids are potent at stimulating CD4+ T cells, in theory they would be useful in detecting the presence of allergen-specific autoimmune T cells in the blood. The CD4+ T cell responses to the Ii-Key assay will evidently help Stallergenes identify which patients would benefit from the specific immunotherapies which they are developing.
The new research article compares the CD4+ T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens. Bet v 1 refers to birch pollen allergen while Der p 1, Der p 2 are considered to be the major allergens derived from house dust mites. The researchers inform that "major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses". A little cheating from Wikipedia tells us that "histocompatibility is the property of having the same, or mostly the same, alleles of a set of genes called the major histocompatibility complex. These genes are expressed in most tissues as antigens, to which the immune system makes antibodies".
The new report from Antigen Express and Stallergenes states that "tetramer+ cells were detected in 19 patients allergic to house dust mites (HDM), seven allergic to birch pollen, 13 allergic to both and nine non-allergics". The report concludes that "different memory CD4+ T cell responses are elicited in the context of chronic vs. seasonal stimulation with the allergen(s). The heterogeneity in the patterns of CD4+ T cell responses observed in patients allergic to HDMs should be taken into account for specific immunotherapy".
A previous peer review published in 2008 by Antigen Express and Stallergenes, titled "Single Cell Assessment of Allergen-Specific T Cell Responses with MHC Class II Peptide Tetramers", revealed that the complex class II peptide tetramers, such as those mentioned in in the new report, were peptides that are "chemically conjugated with the Ii-Key peptide from the MHC invariant chain to facilitate peptide exchange and binding to MHC class II molecules". In the report, the researchers described that the CD4+ T helper cells that are activated to respond to specific allergens can be identified with high sensitivity ex vivo using Ii-Key hybrids. The researchers of the article remarked that Ii-Key peptide tetramers "will also be extremely useful to monitor the efficacy of various immunotherapeutic strategies in humans, using an immunological readout, possibly helping to identify surrogate biological markers of clinical efficacy" and that "Ii-Key conjugate peptides is the most efficient procedure to expand Bet v 1(141-155)-specific CD4+ T cells, allowing to detect such cells in both allergic and healthy individuals".
In April, Stallergenes announced the positive results of a phase III clinical trial conducted in the US for its sublingual grass pollen immunotherapy tablet, Oralair. The Phase III study is the first conducted in the US, after successfully completing four Phase III clinical trials conducted in Europe. Oralair has already been approved by German regulators, and Stallergenes has retained Torreya Partners in hopes of helping them secure a partner for the US market by mid-2011. Stallergenes is currently planning their NDA filing to be submitted to the FDA.
Stallergenes is aware that they also need help in evaluating which patients would most benefit from their allergen immunotherapy tablets, and in their scientific research reports we find evidence that this help may come from an Antigen Express designed assay. Antigen Express' ability to turn their Ii-Key peptide tetramer assay research into a revenue generating asset may not be such a far fetched dream. While that dream remains to be seen, this positive research report concerning Antigen Express' proprietary Ii-Key technology is certainly a step in the right direction.
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