Yukai He, MD, PhD
Dr. Yukai He obtained his MD from Southern Medical University, China, and PhD of Molecular Virology from University of Heidelberg, Germany. He finished his postdoc training in University of Pittsburgh. He's laboratory has been focusing on studying the basic mechanism of genetic immunization with viral vectors and on developing cancer vaccines and immunotherapy for tumors. The research revealed that lentivector could effectively transduce skin dendritic cells (DC), which play a key role in direct priming of naïve CD8 T cells. In 2010, He decided to develop immunological approaches to prevent and treat primary hepatocellular carcinoma (HCC) as the incidence rate of liver cancer has doubled in US.
We are working on developing both the HCC shared antigens and neoantigen cancer vaccines, including the in-situ cancer vaccines released by application of oncolytic virus.
We developed a prime-boost immunization approach to obtain a large number of mouse T cells with highly diverse TCR repertoire and allow us to study the function of activated T cells before identifying the TCR sequence. Through this approach, we have successfully obtained 9 murine TCRs with different affinity for HLA-A2-AFP158 peptide complex. The TCR genes are being used to engineer human T cells to create TCR-T cells that can target and kill HCC tumor cells without causing significant toxicity. The potential antitumor effect in PDX models and orthotopic liver cancer model and possible on- and off- toxicity are being studied. The goal is to acquire sufficient data to determine the possibility of moving TCR-Ts therapies to clinical trials.
To generate more effective and safe CART therapy, we are developing our own antibodies (20 monoclonal antibodies). We fully characterize 7 of them and obtained 3 mAbs that recognize different region of human glypican 3 (GPC3) with high specificity. In addition to investigating the potential diagnostic and therapeutic effect of the GPC3-specific antibodies, we are creating CAR-Ts and investigating the antitumor effect of CAR-Ts using NSG mice and human tumor xenografts. Orthotopic liver cancer model is being developed to allow us to study the CAR-T antitumor effect in a relevant tumor microenvironment. In order to get CAR-Ts work for solid tumors, we need to have a full understanding the governing parameters of T cells and tumor interaction. Thus, CAR-T design and T cell subsets selection are being studied in the lab to get a better grip of how to make CAR-Ts work for solid tumors.
Hong Y, Peng Y, Guo ZS, Guevara-Patino J, Pang J, Butterfield LH, Mivechi NF, Munn DH, Bartlett DL, *He Y. Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma. Hepatology. 2014 Apr; 59(4):1448-58.
Wu S, Zhu W, Peng Y, Wang L, Hong Y, Huang L, Dong D, Xie J, Merchen T, Kruse E, Guo ZS, Bartlett D, Fu N, He Y* The Antitumor Effects of Vaccine-Activated CD8+ T Cells Associate with Weak TCR Signaling and Induction of Stem-Like Memory T Cells. Cancer Immunol Res. 2017, 5(10): 908-12.
Zhu W, Peng Y, Wang L, Hong Y, Jiang X, Li Q, Liu H, Huang L, Wu J, Celis E, Merchen T, Kruse E, He Y. Identification of α-fetoprotein-specific T cell receptors for hepatocellular carcinoma immunotherapy. Hepatology. 2018 Aug; 68(2):574-589. doi: 10.1002/hep.29844. Epub 2018 Jun 12.
Wang W, He Y, Wu S. Harnessing the CD8+T-cell subsets with stemness for tumor immunotherapy. Future Oncol. 2018 Aug 24. doi: 10.2217/fon-2018-0238.
Guo ZS, Lu B, Guo Z, Giehl E, Feist M, Dai E, Liu W, Storkus WJ, He Y, Liu Z, Bartlett DL. Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics. J Immunother Cancer. 2019 Jan 9; 7(1):6.