Abstract:. Our research has focused on understanding the mechanism that explains this mutual protection between cancer and AD, and to this end we developed an animal model. We found that the generation of a tumor by injecting melanocytic cells into a mouse transgenic for AD (5xFAD) causes a decrease in AD neuropathology in the brain (a decrease in the No of beta amyloid plaques), in addition to reduced tumor growth, compared to animals without AD (littermates without the AD mutations). The fact that a subcutaneous tumor has an effect at the brain level suggests that there is a circulating factor that mediates this effect and the immune system is a good candidate. Drs. F. Salazar and M. Lopez in our country have developed a vaccine (TRIMELVax patent US9694059) based on a tumor lysate from a mixture of three allogeneic human metastatic melanoma cell lines plus an adjuvant called CCH, with promising results in the treatment of cancer (melanoma and prostate) through the activation of the immune system. We propose to validate this vaccine as a new effective immunotherapy for the treatment of Alzheimer’s disease. In the 5xFAD mouse, the vaccine or placebo will be injected subcutaneously, 1 weekly dose (for 3 or 6 weeks) administered at two times of the disease: before the development of symptoms (at 3 months of age) and after the onset of symptoms (6 months of age), in order to know its preventive and therapeutic effect. The expected responses with the use of this product in the treatment of AD are: 1) To stimulate the body’s immune system by conferring an increased pro-inflammatory state that prevents the formation or triggers the elimination of toxic deposits of beta amyloid protein in the brain; 2) That the above translates into cognitive improvement (assessed by memory/behavioral tests) and 3) That the effect of the treatment is maintained thanks to the phenomenon of immunological memory, allowing the disease to stop or considerably slow its progression over time. Since the results of this project could give rise to a new use for this vaccine, it is planned to request a modification of use of the TRIMELVax patent. The entities associated to this project are: the biotechnological company Oncobiomed and Clínica Las Condes, the former is interested in receiving the transfer of the product and the latter hopes to be able to contribute to the development, foreseeing an opportunity to participate in its therapeutic provision in the future. Advancing towards an effective treatment for AD is urgent and this innovative proposal has the scientific background and the qualified team to achieve it.
Director: Maria Isabel Behrens
Co-PI: Claudia Duran-Aniotz
Support: ANID/FONDEF
