Identification of Tumoricidal T Cell Receptors from Hepatocellular Carcinomainfiltrating CD8+ T Lymphocytes

JI Program: Cancer

Hepatocellular carcinoma (HCC) is an aggressive malignancy whose poor prognosis is driven
in part by a lack of curative treatment options. We previously cloned three novel HCC-specific
murine T cell receptor (TCR) genes that can redirect human T cells to effectively eliminate HCC
tumor cells, demonstrating the potential to engineer a patient’s autologous T cells to treat HCC.
In addition, we have isolated specific CD8+ tumor infiltrating lymphocytes (TILs) from HCC patients
and observed their potent antitumor function after in vitro proliferation. In this project, we seek
to infuse CD8+ TILs derived from HCC patients into immunodeficient mice harboring autologous
HCC, and subsequently clone TCR genes from patient-derived CD8+ T cells with antitumor
phenotype. Following validation of their functions, we will determine their targeted tumor antigens
through epitope prediction algorithms and unbiased screening using yeast-display libraries.
In sum, we will identify novel tumoricidal TCR genes from HCC CD8+ TILs, thereby engineering
patient-derived autologous T cells to generate potently tumoricidal TCR-T lymphocytes to treat
HCC patients.