Fang-Wei

Research area:                                                                                                           GroupPro>>
1.The biology of PD-1/PD-L1 and its potential application in adoptive T cell therapy when combining with chimeric antigen receptor
The specificity and efficiency of cytotoxicity T lymphocyte determines the outcome of immune therapy to cancer patients or the ones with chronic infection. High curative potential of adoptive transfer with chimeric antigen receptor modified T cells in patients with metastatic melanoma and more recently B-lineage malignancies has stimulated attempts to apply this approach to treat other cancer types. In the other hand, the continued presence of antigen subverts normal memory T cell generation and upregulates its negative regulator gene program death-1 (PD-1), then leads effector T cells down a path of exhaustion. The blockade of immune check point gene PD-1 has great promise in cancer immunotherapy. We are interested in elucidating the potential of CAR and PD-1 combined adoptive T cell transfer treatment in triple negative breast cancers and anaplastic large cell lymphoma model.  
2.Mechanisms of oncogene Anaplastic Lymphoma Kinase (ALK)-induced T cell tumorigenesis Chromosome rearrangement in anaplastic lymphoma kinase (ALK) loci has been described in a wide range of cancer types. Clinical results and data from transgenic mouse models had clearly shown that ALK is involved in the tumor initiation and progression. However, it is not fully understood how does ALK become a ‘trouble maker’ in the context of human tumors? In our previous study, we have demonstrated that in vitro transduction of normal human CD4+ T lymphocytes with NPM-ALK resulted in their malignant transformation. The transformed cells become immortalized and display morphology and immune-phenotype characteristic of patient-derived anaplastic large-cell lymphomas in vitro and in vivo. Interestingly, the NPM-ALK immortalized cells are clonal. Our model closely recapitulated the features of the native tumors that can be faithfully reproduced in vitro, which permit our further study of the early stages of carcinogenesis. In his proposal, we would utilize this model to study how ALK induce malignant cell transformation. We will also analysis antigens associated with ALK rearranged anaplastic large cell lymphoma and non-small cell lung cancer, and further develop antigen specific chimeric antigen receptor (CAR) modified T cells, to target the tumors utilizing adoptive T cell transfer (ACT) in in vitro and in vivo models. Our purpose of this study is to understand mechanistic insight to ALK-induced oncogenesis, and further to provide new targets and methods in cancer early diagnose and controlling.

Publications

1. Wang C, Zhu C, Wei F, Zhang L, Mo X, Feng Y, Xu J, Yuan Z, Robertson E, Cai Q. Constitutive Activation of Interleukin-13/STAT6 Contributes to Kaposi's Sarcoma-Associated Herpesvirus-Related Primary Effusion Lymphoma Cell Proliferation and Survival. J Virol. 2015, 89(20):10416-26.
2. Gan J, Wang C, Jin Y, Guo Y, Xu F, Zhu Q, Ding L, Shang H, Wang J, Wei F, Cai Q, Robertson ES. Proteomic profiling identifies the SIM-associated complex of KSHV-encoded LANA. Proteomics. 2015, 15(12):2023-37.