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CMV-CD19 bi-specific CAR T cells with CMV vaccine as post-transplantation immunotherapy for ALL

Ryotaro Nakamura

Ryotaro Nakamura


Beckman Research Institute of the City of Hope

Project Term: July 1, 2019 - June 30, 2022

We propose to develop an innovative adaptive cellular immunotherapy (ACIT) utilizing Chimeric Antigen Receptor (CAR)-engineered T cells, which respond to both CD19+ cells and cytomegalovirus (CMV) antigen, namely CMV-CD19 bi-specific T cells, followed by CMV vaccine to further expand the T cells in vivo. We aim to address the unmet need to improve high relapse rate in patients with ALL undergoing hematopoietic cell transplantation (HCT) from a matched or mismatched unrelated/related donors.

Lay Abstract

Disease relapse is the most frequent cause of treatment failure and mortality after hematopoietic cell transplantation (HCT) in patients with acute lymphoblastic leukemia (ALL). Cancer immunotherapy, is a type of cancer treatment that boosts the body natural defense to fight cancer. The method entails isolating patient’s immune cells (T cells) and genetically engineering them to recognize and kill cancer cells using a Chimeric Antigen Receptor (CAR). By infusing these CAR T cells back into the patient, the engineered cells seek out and eliminate malignant cells. However, the full potential of CAR T therapy is hampered by the lack of long-term persistence of the engineered T cells in patients. Here, we propose to utilize CAR-engineered T cells, which respond to both leukemic (CD19+) cells and cytomegalovirus (CMV) antigen, namely CMV/CD19 bi-specific T cells, followed by CMV vaccine (Triplex), recently developed and clinically evaluated at City of Hope, to further expand the T cells in vivo in ALL patients who underwent allogeneic HCT. The proposed strategy is design to enhance proliferation, lengthen persistence and augment the anti-lymphoma activity of adoptively transferred CMV-CD19 CAR T cells. Completion of this study has the potential to improve the progression-free survival in patients with AML. It is also expected to provide critical information to further develop this immune cell-based therapy for treatment of multiple other malignancies.

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