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.