Generex Biotechnology has published studies conducted at the Mayo Clinic using the Antigen Express proprietary Ii-Key technology. Antigen Express, Generex’s 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, single-blinded phase II clinical trial in patients with HER-2 expressing breast cancer.
The publication, entitled "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.
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. 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. It was found that AE37 was the only peptide able to generate an immunological response when administered without an adjuvant (co-stimulatory agent). AE37 also was the only peptide shown to decrease the level of T regulatory cells.
The study endpoint of the current phase II trial of AE37 is a reduction in cancer relapse after two years compared to the current standard of care treatment. There are currently over 200 patients enrolled in the study with either 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.
It is anticipated that a phase III trial will be conducted in this specific patient population having low-to-intermediate HER-2 expression levels.