CS1 Chimeric Antigen Receptor (CAR) T Cells for Treatment of High-Risk Multiple Myeloma

Multiple myeloma (MM) is the second most frequent blood cancer in developed countries, with effective treatments for most, but those patients with high-risk disease will quickly succumb to the disease. Unprecedented success has recently been reported in other blood cancers with the use of cellular therapeutic targeting via the technology “chimeric antigen receptors (CAR)”, involving the infusion of genetically engineered T cells, which are targeted towards proteins on the tumor cell surface, into relapsed patients. Once infused, these targeted cells expand on encountering myeloma cells, killing the myeloma cells in the patient regardless of the myeloma cell resistance to prior therapies.

In this application, based on our published preclinical data with this technology, we propose the final cell manufacturing steps in preparation for a CAR clinical trial, targeting a myeloma surface protein, CS1, in relapsed myeloma patients. This technology should apply to any myeloma patients who have this protein on the surface of their tumor cells. In fact, tumor cells in 95% of all myeloma patients have this protein on their surface. Thus, the technology that we have developed can be used to treat the majority of myeloma patients.

We will also test whether these CAR cells that we have developed are safe, by testing them against a wide range of human cell lines (liver, kidney, spleen, heart, brain, etc) and by using immunologically competent mouse models. We also add a suicide gene to our CAR T cells so that it can be removed from patients after all tumors are removed or if we found they are highly toxic to patients after infusion of the CAR cells. Our ultimate goal is to bring safe CS1-CAR T cells into the clinic in next 2-3 years.

Thus, in this study, we aim to optimize our CS1-CAR T cells and develop a next–generation treatment for high-risk or relapsed myeloma patents.

English
Grant Id: 
20298222
Grant Workflow State: 
Grant Subprogram Id: 
Grant Start Date: 
Friday, September 30, 2016 - 20:00
Grant End Date: 
Sunday, September 29, 2019
Investigator First Name: 
Jianhua
Investigator Last Name: 
Yu, PhD
Organization State: 
Investigator State: 
Organization Country: 
Investigator Country: 
Organization City: 
Columbus
Investigator Zip Code: 
43210
Organization Zip Code: 
43210
Organization Name: 
The Ohio State University
Spending Year: 
2016
Contract Number: 
6503-17
Investigator Full Name: 
Jianhua Yu, PhD