In collaboration with MIND institute (Dr. D. Cribbs’ Group) we developed and tested several DNA and peptide based Alzheimer’s disease (AD) epitope vaccines. The most effective DNA epitope vaccine in AD mouse models is currently tested in non-human primates with purpose to translate it into clinical testing. In parallel we are continuing to improve the efficacy of DNA epitope vaccine, immunization protocols, delivery of DNA in different animal models.
UCI, Institute for Immunology
In collaboration with the Institute for Immunology at UCI (Dr. E. Nelson’s Group) we are working on development of breast cancer vaccine based on novel cancer-testis (CT) antigen BORIS and tumor-associated antigen Her2/Neu in rat and mouse models. The synergistic effect of vaccination with two antigens in combination with agents inhibiting the activity of immune suppressor cells may lead to the development of an effective vaccine formulation for treatment of breast cancer patients.
Laboratory of Immunopathology, NIAID, NIH
Collaboration with the Laboratory of Immunopathology at NIAID led to the development of cancer vaccine based on a novel cancer-testis (CT) antigen, the Brother of the Regulator of Imprinted Sites (BORIS) identified by Dr. Lobanenkov’s Group as a mammalian paralogue of CTCF. Many advantages over the other tumor associated antigens make BORIS very attractive candidate for cancer vaccine development: BORIS expression in normal tissues is restricted to testis; BORIS is detected in a very high percentage of histologically unrelated primary tumors & tumor cell lines including ~70.7% of breast cancers; BORIS expression is important for activation of other CT genes such as MAGE-A1, NY-ESO-1 etc; BORIS protein is important for the tumor cell viability and malignant phenotype: it has cell-transforming activity and compete with tumor-suppressor CTCF for DNA target sites. We demonstrated the immunological and therapeutic potency of BORIS vaccines based on DNA or Dendritic Cells in very aggressive 4T1 breast cancer mouse model.
Ichor Medical Systems
DNA vaccines have generally exhibited low and inconsistent immune responses in clinical studies due to the low delivery efficiency characteristic of current DNA administration technologies. Electroporation (EP) dramatically increases the efficiency of delivery of DNA into cells improving the potency of DNA vaccines by 10-1000 fold compared to conventional injection methods. The integrated, fully automated administration device for EP mediated i.m. DNA vaccine delivery (TDS-IM) has been developed by Ichor Medical Systems. We are effectively collaborating with Ichor Medical Systems, Inc. in testing the safety and immunogenicity of Alzheimer’s disease (AD) DNA epitope vaccine delivered by TDS-IM in non-human primates. The successful completion of this project will bring the AD DNA vaccine into clinical testing.
The immunogenicity of DNA vaccine could be enhanced by combination of molecular and conventional adjuvants. Iomai, Inc. (currently acquired by Intercell) developed LT (Escherichia coli heat-labile enterotoxin) adjuvant-laden immunostimulatory (IS) patches (Iomai, Inc.) and demonstrated that the application of these patches at the site of protein vaccine inoculation resulted in 10- to 50-fold increases in the influenza virus-specific immune response. In collaboration with Iomai, Inc. we demonstrated that the LT-IS patches increase the efficacy of DNA vaccines delivered by gene gun. Presently we are working on improvement of Alzheimer’s disease (AD) DNA epitope vaccine by combination of LT-IS patches and the best DNA delivery system. The success in this study may lead to development of a safe and effective DNA epitope vaccination protocol for pre-clinical trials in monkeys before moving to clinical trial in elderly AD patients. In addition, we are testing the efficacy of LT-IS patches for activation of immune responses against various protein vaccines.
In collaboration with Advaxis, Inc. we are working on development of new and effective cancer vaccines based on a novel cancer-testis (CT) antigen, the Brother of the Regulator of Imprinted Sites (BORIS) delivered by bioengineered bacterium, Listeria monocytogenes capable of stimulating cellular immune responses and altering tumor microenvironments to allow the immune response to work.
Lundbeck, Inc. is one of the biggest research-based companies in the world engaged in research to find new drugs for treatment of CNS disorders, including depression, schizophrenia, Alzheimer’s disease, Parkinson’s disease and insomnia. We are collaborating with Lundbeck, Inc. on testing the efficacy of new Alzheimer’s disease vaccines generated in this company.