The American Cancer Society estimates that this year in the United States, there will be 268,490 new cases of prostate cancer. It also estimates that 34,500 men will die from the cancer in 2022. Other than skin cancer, prostate cancer is the most common cancer in American men.
These stark statistics are why the California Institute for Regenerative Medicine (CIRM) has awarded a $5.8 million grant to researchers at the University of Southern California to begin conducting preclinical studies using an innovative treatment for prostate cancer, known as synthetic immune receptor (SIR-T) therapy.
“We have a homegrown USC technology which shows a lot of promise. If the path that we are on ultimately proves successful, it could revolutionize the treatment of not only prostate cancer but also other cancers,” said principal investigator Dr. Preet M. Chaudhary, a professor of medicine at the Keck School of Medicine of USC.
A new approach to immunotherapy
CAR-T cell therapy—which is now approved by the U.S. Food and Drug Administration (FDA) to treat several blood cancers—has been revolutionary for certain patients. In CAR-T therapy, a patient’s T-cells—a key part of their immune system—are extracted and genetically engineered to express the chimeric antigen receptor (CAR). The modified T-cells are then reinjected into the patient, where CAR enables them to selectively seek out, bind to, and kill cancer cells.
But its success in treating blood cancers has not translated into effectiveness against solid tumor cancers, such as prostate, breast, brain, gastrointestinal, skin and lung cancer.
“The bottom line is that people have tried to replicate the success of CAR-T cell therapy with solid tumor cancers, and have been mostly unsuccessful,” Chaudhary said.
SIR-T therapy, in contrast, uses different receptors that more closely resemble the body’s natural T-cells. Chaudhary and his team tested thousands of prototypes over an eight-year period to develop receptors that are effective and safe for solid tumors, including prostate cancer. An initial round of tests in mice yielded very promising results, prompting Chaudhary to apply for funding from CIRM.
What’s next?
With CIRM funding, Chaudhary and his team can now begin conducting preclinical trials of SIR-T therapy. Their research over the next two and a half years will culminate in an application for FDA approval to begin clinical trials in humans.
Chaudhary’s lab is also testing SIR-T therapy for other types of cancer, including melanoma, kidney cancer, lymphoma and a different molecule involved in prostate cancer.
“This technology has a lot of different applications, so we are working to ensure the platform works across disease types,” Chaudhary said. “The series of grants we’ve received reflects a lot of excitement about the SIR-T platform.”
To learn more about the work CIRM has funded to better understand solid tumors, visit our Solid Tumor Fact Sheet web page.
The Stem Cellar 
In vertebrates, both humoral and cellular immunity require foreign antigens to induce specific responses. Although a complex interaction of many distinct cell types and a host of biologically active soluble mediators contribute to inflammatory response. However, only two cell types interact in a highly specific manner with foreign antigens to initiate the immune response. B lymphocytes and T lymphocytes accomplish this through the use of highly diverse protein complexes on their cell surfaces which act as antigen receptors. Hence, membrane-bound immunoglobulin act as B-cell receptor for antigen, wheras specific T-cell antigen receptor, such as αβTCR are determined to be associated with a complex of invariant chains called CD3 on the cell surface. In immune cells, there is immunoreceptor tyrosine-based activation motif(ITAM) in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors. ITAM signaling is required for both innate and adaptive immunity. It also regulate the function of myeloid cells such as macrophages, neutrophils and dendretic cells. Each αβT-cell receptor contain 10 ITAMs (CD3-gamma, -beta, -epsilon & TCR-zeta). Phosphorylation of ITAMs enhance the receptor signaling which has consequent impact on activation of cytoplasmic pathways. Different levels of ITAMs phosphorylation induce diverse cellular response such as differentiation, proliferation, behavior and functioning. Therefore, the activation of immune cells are closely related with phosporylation of ITAMs. Evidence proved that chimerization of receptor failed to activate phosphorylation of ITAMs and induced weaker association between αβ heterodimer and CD3 complex. The production of weaker immune cells resulted inhibition of calcium mediated signaling pathway. Although the mutant TCR still bind the ligands but fail to transmit a complete signal to the cell. Current investigation on CAR-T cell showed high efficiency of cancer therapy in blood cancers but not in solid tumors. The finding indicated that modification of receptors on T cells induced incomplete receptor-cellular signaling which inhibited CAR-T cells from extravasation into solid tumor. Further investigation to determine ability of SIR-T cells to produce complete receptor-cellular signaling which can substantially improve the efficiency of cancer therapy on solid tumors