Kole Roybal, PhD

Assistant Professor
Department of Microbiology and Immunology
Parker Institute for Cancer Immunotherapy
Helen Diller Family Comprehensive Cancer Center
+1 415 476-8289

Recent clinical trials have demonstrated the remarkable promise of adoptive T cell immunotherapy for cancer. T cells engineered to express chimeric antigen receptors (CARs) - artificial receptors containing an extracellular antibody against a tumor antigen, fused to the intracellular region of the native T cell receptor - are able to target and kill certain leukemias. The major challenge facing these innovative therapies, however, is the lack of control over these engineered cells; cross-activation and hyperactive immune responses have led to severe adverse effects in patients. In the case of solid tumors, T cell therapies have been largely ineffective due to problems with infiltration of the cells into the tumor and immunosuppressive tumor microenvironments. Thus, the safety and effectiveness of T cell therapies must be improved in order to expand their therapeutic utility.

With these challenges in immune cell therapeutics in mind, the Roybal lab harnesses the tools of synthetic and chemical biology to enhance the therapeutic potential of engineered immune cells. We take a comprehensive approach to cellular engineering by developing new synthetic receptors, signal transduction cascades, and cellular response programs to enhance the safety and effectiveness of adoptive cell therapies. We also study the logic of natural cellular signaling systems, and the underlying principles of cellular communication and collective cell behavior during an immune response. These interests are complimentary as cell engineering is often informed by knowledge obtained from studying natural mechanisms of cell regulation refined by evolution.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Control and Customization of Immune Cell Responses: Engineering new synthetic receptors, signal transduction cascades, and immune cell behaviors for cell therapies for cancer and autoimmunity

Websites

Featured Publications: 

Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors.

Cell

Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I, Choe JH, Walker WJ, McNally KA, Lim WA

Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits.

Cell

Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, Lim WA

Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors.

Cell

Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, Lim WA

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.

Science (New York, N.Y.)

Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA

Computational spatiotemporal analysis identifies WAVE2 and cofilin as joint regulators of costimulation-mediated T cell actin dynamics.

Science signaling

Roybal KT, Buck TE, Ruan X, Cho BH, Clark DJ, Ambler R, Tunbridge HM, Zhang J, Verkade P, Wülfing C, Murphy RF