Cell Therapy

Investigator

Engineering immune cells to Treat Cancer

Jino Park, Ph.D.

The immune system - B, T, and NK cells – is the body’s defense against infection and cancer1. The most promising treatment for blood cancer is chimeric antigen receptor (CAR)-T cell therapy. This immunotherapy uses own immune system to help fight cancer.

Adoptive transfer of human T cells expressing engineered receptors has shown great promise in treating human cancers. Chimeric antigen receptor (CAR) T cell therapy represents a major advancement in personalized cancer treatment. In this strategy, a patient’s own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. CAR T cells are then produced and expanded in a Good Manufacturing Practice (GMP) facility for clinical use, and then infused back into the patient’s body2. Recently, CD19 CAR T cell therapy was approved as a “breakthrough cancer therapy” for children and young adults by the US FDA due to its remarkable efficacy in relapsed/refractory B cell malignancies bearing the CD19 surface antigen3.

Despite the success of CAR-T therapy for B cell Acute Lymphoblastic Leukemia (ALL), several hundred patients still die of this cancer each year. After ALL, Acute Myeloid Leukemia (AML) is the second most common killer of patients suffering from leukemia. Given that patients suffering from these two devastating leukemias have limited options once standard therapies have been exhausted, we are proposing to develop novel CAR T cells to treat refractory B cell ALL and AML. To accomplish these goals, we will propose to enhance our infrastructure for the testing of genetically engineered cellular immunotherapies not only for B cell ALL and AML patients but also for patients suffering from multiple other types of cancers.

Specifically, we envision the creation of a GMP facility to produce genetically engineered CAR T cells that will be made available in clinical trials at MetroHealth, as well as at other regional hospitals that are caring for cancer patients. Our specific aims are to: (i) Standardize the GMP operation to ensure CAR T cell manufacturing quality and safety needed for future IND applications and for patients to be enrolled into clinical trials; and (ii) Optimize the manufacturing engineering runs for the dual targeted CAR T cells for and VAC CAR T cells for lymphoid malignancies and submit both IND applications to the FDA4. Our development operations are focused on creative and efficient paths to bring novel, cost-effective therapies to patients. We continue to advance the field by researching to develop more CAR cell drugs.

MetroHealth will conduct clinical trials supported by our state-of-the-art GMP facility to manufacturing precision-based therapeutics to improve the health and wellness of our community.

References

Sadelain, M. CD19 CAR T Cells. Cell 171, 1471 (2017).
Gee, A.P. GMP CAR-T cell production. Best Pract Res Clin Haematol 31, 126-134 (2018).
Tisagenlecleucel (Kymriah) for ALL. Med Lett Drugs Ther 59, 177-178 (2017).
Mizrahi, R.A., et al. GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2. Pathogens 11(2022).