Generex Publishes Studies Confirming & Extending the Antigen Express Ii-Key Platform Technology
Generex Biotechnology Corporation recently announced the publication of studies conducted at the Mayo Clinic using the Antigen Express proprietary Ii-Key technology. Antigen Express, Inc., the company’s wholly owned subsidiary, has used this technology platform in the development of self-potentiating immunotherapeutic vaccines for cancer. AE37, an Ii-Key HER-2 hybrid, is currently the subject of a controlled, randomized, and single-blinded Phase II clinical trial in patients with HER-2 expressing breast cancer.
The publication, MHC Class II Epitope Nesting Modulates Dendritic Cell Function and Improves Generation of Antigen-Specific CD4 Helper T Cells, was published in the peer-reviewed Journal of Immunology. A significant finding of the report, conducted in a mouse model, was that specific CD4+ T cell (T-helper) activation by Ii-Key hybrids excludes T regulatory (immune suppressor) cells. T regulatory cells (immune suppressor) may hinder active immunotherapy of cancer. The lack of activation of this cell type has been observed previously in clinical studies of AE37 (an Ii-Key-HER-2 hybrid), both in breast as well as prostate cancer patients.
The senior author of the study, Dr. Keith Knutson, has been one of the pioneers in the field of CD4+ T-helper cell stimulation for active immunotherapy of cancer. “We are pleased to see this further confirmation of the potential of our technology,” said Dr. Eric von Hofe, President of Antigen Express. “Dr. Knutson has been one of the most important leaders in the field. The confirmation of the lack of T regulatory cell activation, known to have immune suppressive effects, adds to our prior findings and suggests Ii-Key hybrids could have potential in the field of cancer immunotherapy.”
“This study further supports the differentiating profile of AE37 with other cancer immunotherapies and provides additional momentum to AE37’s clinical development,” added Jos van der Woert, who has accepted the position of Chief Executive Officer of Antigen Express.
Prior clinical studies of an Ii-Key hybrid peptide being developed by Antigen Express, AE37, including a Phase I trial in patients with prostate cancer and a separate trial in patients with breast cancer, have been reported as the subject of four publications in leading peer-reviewed journals. In brief, those studies showed that AE37 is safe, well-tolerated, and produced immunological responses that were above-and-beyond what had been hoped for. When compared with two other HER-2 vaccines that have been evaluated in the clinic, AE37 produced the greatest HER-2-related delayed-type hypersensitivity (DTH) reactions in immunized patients. Of all immunological responses examined in patients undergoing active immunotherapy for cancer, it has been argued that a strong DTH response most reliably predicts efficacy. In addition, it was found that AE37 was the only peptide able to generate an immunological response when administered without an adjuvant (co-stimulatory agent). Finally, (as previously indicated) AE37 also was the only peptide shown to decrease the level of T regulatory cells.
A controlled, randomized, and single-blinded Phase II clinical study of AE37 in HER-2 expressing breast cancer patients is currently underway to establish clinical efficacy. The study endpoint is a reduction in cancer relapse after 2 years compared to the current standard of care treatment. There are currently over 200 patients enrolled in the study with node positive or high-risk node-negative breast cancer. While positive preliminary results suggested that statistically definitive results may be obtained in 2012, it was decided to enroll an additional 100 patients early in 2011 to ensure sufficient patient numbers. In particular, these additional patients are required to have low HER-2 expression levels such that they are not eligible for Herceptin. Although 75% of breast cancer patients have some level of HER-2 expression and are eligible for AE37, only 25% have HER-2 levels high enough to be eligible for Herceptin. The population of patients with low-to-intermediate levels of HER-2 expression currently has no treatment option. For this reason, it is anticipated that a Phase III trial will be conducted in this specific patient population having low-to-intermediate HER-2 expression levels.
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