Shiladitya Sengupta, Ph.D.

In the search for a cure for lung cancer, several promising approaches have emerged. These include the development of molecularly-targeted treatments that block cancer pathways; the use of immune checkpoint inhibitors to activate the immune system against cancer cells, and the use of nanotechnology to target cancer. Nanotechnology manipulates matter at the molecular level. We will explore a novel treatment that combines all three approaches. We will engineer two next-generation nanoparticles. They can combine a phosphatidylinositol 3 kinase (PI3K) inhibitor a drug that inhibits PI3K enzymes, which are involved in cancer growth, with immune checkpoint inhibitors that activate immune cells against lung cancer. The PI3K can increase the response to the immune checkpoint inhibitors. This approach may result in a significant advance in treatment of lung cancer, which can lead to improved outcomes with reduced side effects.

Update:

We have found that the concept of targeting lung cancer with targeted and immune checkpoint inhibitors is working, and resulting in greater potency. Lung cancer cells express high levels of immune checkpoint molecules called PDL1 and CD47, which can inactivate T cells and macrophage immune cells, respectively. In year one of this project, we have engineered a novel PI3K-inhibiting nanoparticle (TS-70);  demonstrated that PI3K inhibition by PI103 and TS-70 increases the expression of PDL1 and CD47 in lung cancer, which is essential to attract more PDL1 and CD47-targeted nanoparticles to the tumor; engineered a PI3K-inhibiting nanoparticle with dual anti-CD47 and anti-PDL1 antibodies for targeting cancer cells; and demonstrated these nanoparticles are effective in a test tube model compared with the PI3K inhibition alone.