Department of Melanoma Medical Oncology, Division of Cancer Medicine，The University of Texas MD Anderson Cancer Center

Our lab has been engaged in the study of tumor immunology and adoptive cellular therapy over the last 18 years. We have focused our research towards an understanding of human T cell biology, anti-tumor immunity and the development of translational strategies which we have applied to several first-in-man studies of adoptive cellular therapy (ACT). We pioneered Endogenous T Cell (ETC) therapy using peripheral blood as a source of T cells for ACT and the  use of IL-21 for generating longlasting central memory-type T cells. Our lab established several protocols using a combination of adoptive cellular therapy and immune modulation (immune checkpoint inhibitors, costimulatory agonists, oncolytic virotherapy) and demonstrated that durable clinical responses can be achieved in patients with refractory solid tumor malignancies without serious adverse toxicities.   A major focus in our lab is to investigate combination strategies of checkpoint blockade and adoptive T-cell therapy for the treatment of cancers such as uveal melanoma and pancreatic cancer. A second major focus has been the development of an antigen discovery pipeline to identify and fully validate immunogenic targets for cell therapy.  

Over the course of 18 years, we developed specialized strategies to isolate and expand from the peripheral blood of patients antigen-specific T cells for adoptive therapy. We first demonstrated that these often rare (< 1:100,000) tumor-reactive T cells exist in the peripheral blood of patients with cancer, and then developed enabling technologies, to isolate and expand such T cells, with high proliferative capacity for downstream studies for clinical trials . Using methods developed in our lab, we were able to implement several first-in-human clinical trials using well-defined effector populations including antigen-specific CD8 T cell clones, CD4 T cell clones, and IL-21-primied central memory T cells targeting liquid and solid tumor-associated antigens for the treatment of patients with advanced cancer, and to use these transferred effector cells in combination with immunomodulatory compounds including immune checkpoint inhibitors and vaccines. The over-arching goal of this approach was to dissect the reasons for success and failure to facilitate the design of next generation studies and to provide a means of delivering such therapies to as many disease types and patients as possible. To this end, we have utilized cutting edge technologies that will eventually provide point-of-care ACT to patients with solid tumor mlaignanices including melanoma sarcoma, and lung ovarian, breast, pancreatic, gastric and colorectal cancers.

A lot of research papers from Yee’s team were published in the top journals such as Nat Med J Exp Med, N Eng J Med , J Clin Oncol Sci Immunol, PNAS, J Immunol, J Immunother Cancer, Cancer Immunol Res.et al