Methods to increase cellular therapy resistance against immune suppression in cancer


The current state of the art:


Anti-tumor immune therapy enhances the human immune response to inhibit tumor growth. Cellular therapy such as CAR T therapy boosts the natural ability of T cells and improves survival time in blood cancer. On the other hand, the immune system is also regulated by negative factors-immune checkpoint such as PD1 and CTLA4. Inhibitors of PD1 and CTLA4 have been improved by the FDA to treat a variety of cancer types. 


The problems with the current art:

However, a lot of patients do not respond to these immune therapies or develop resistance ultimately. In solid tumors, the efficacy is still limited. Therefore, exploitation of other checkpoint receptors that may induce T cell dysfunction and inhibit anti-tumor immunity are needed. 


The advantages of our invention:

The scientists at AU developed a novel method to reverse the immune suppression and enhance cellular therapy by simultaneously inhibiting the expression of multiple immune negative regulators including DR5, Tim3, and TGFbeta. In the animal study, simultaneous inhibition of DR5, Tim3, and TGFbeta in T cells improved the survival time and caused tumor regression. It improved the CAR-T cell efficacy by further decreasing the tumor growth compared to CART-t cell alone. Moreover, the current method works synergistically with the PD-1 inhibitor in the melanoma mice model by improving survival time. Therefore, the current method can be a promising option to better the anti-tumor immunity to treat cancer.


AURI 2019-019

IP status: US provisional application


Patent Information:
For Information, Contact:
Lei Wan
Technology Transfer Associate
Augusta University
Pandelakis Koni
Esteban Celis
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