Targeting PIM Kinase with PD1 Inhibition Improves Immunotherapeutic Antitumor T-cell Response
Abstract
Adoptive T-cell therapy (ACT) of cancer, which involves the infusion of ex vivo–engineered tumor epitope reactive autologous T cells into the tumor-bearing host, is a potential treatment modality for cancer. However, the durable antitumor response following ACT is hampered either by loss of effector function or survival of the antitumor T cells. Therefore, strategies to improve the persistence and sustain the effector function of the antitumor T cells are of immense importance. Given the role of metabolism in determining the therapeutic efficacy of T cells, we hypothesize that inhibition of PIM kinases, a family of serine/threonine kinase that promote cell-cycle transition, cell growth, and regulate mTORC1 activity, can improve the potency of T cells in controlling tumor.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2019
- Source ID
- 10.1158/1078-0432.ccr-18-0706
Entities
People
- Andrew S Kraft
- Anusara Daenthanasanmak
- Carsten Krieg
- Craig C. Beeson
- Elizabeth G. Hill
- Gabriela Andrejeva
- Jeffery C. Rathmell
- Libia A. Luevano
- Meenal Mehrotra
- Melissa Wolf
- Paramita Chakraborty
- Shikhar Mehrotra
- Shilpak Chatterjee
- Supinya Iamsawat
- Uday Baliga
- Xue-zhong Yu
Organizations
- Hollings Cancer Center
- Medical University of South Carolina
- National Institutes of Health
- United States Department of Defense
- University of Arizona
- University of Arizona Cancer Center
- Vanderbilt University