Reprogramming Tumor Reactive T Cells

Improving understanding and treatment therapies for high-risk hematological malignancies

Full Project Name:Reprogramming Tumor Reactive T cells to Treat High Risk Hematological MalignanciesPrincipal Investigator:Weiguo Cui, PhD, Microbiology and ImmunologyCo-Investigator:Bryon D. Johnson, PhD, Medicine; Ehab L. Atallah, MD, MedicineAward Amount:$200,000

Award Date

February2017

Project Duration:24 months

Project Description Narrative:

In 2015, the American Cancer Society estimated that more than 56,000 deaths in the U.S. were due to hematologic malignancies (leukemias, lymphomas, and myeloma), and that many of these deaths were attributable to the high-risk hematologic malignancies. Innovative approaches, including immunotherapies such as adoptive T cell transfer (ACT), are needed to ensure the complete and durable regression of these diseases. However, such an approach is often curtailed because tumor-reactive T cells become functionally exhausted.

To overcome this fundamental problem, new knowledge is needed to understand the genetic pathways that govern the differentiation state of T cell exhaustion in order to identify key targets to reprogram and restore their function for more effective immunotherapy. Through this award, researchers aim to reprogram the tumor reactive CD8 T cells by epigenetic modifications to restore and enhance their anti-tumor function in treating high-risk hematological malignancies.

Outcomes & Lessons Learned:

• Gained knowledge that some subsets of T cells are more easily "programmed" to recover antitumor immunity than others

• This new knowledge provides mechanistic insights for therapeutic designs that are applicable to many types of cancer

• Findings from this project can be translated to clinical care rather quickly to start benefitting cancer patients locally

• Awarded external funding to continue research

• Published three manuscripts and presented findings internationally

Project Updates:

• Gained knowledge that the killing function of tumor reactive T cells can be restored

• Began exploration of how key gene regulation machinery in tumor-reactive T cells can be exploited by genetic engineering to potentially revitalize dysfunctional T cells and enable them to kill tumor cells as a means of immunotherapy