1 .Differential Regulation by IL-4 of Protein Tyrosine Phosphorylation in IL-2-induced LAK cells and `CD3-induced CD3-AK Cells and the Correlation with their Cytolytic Activity. Our study shows that IL-2-induced T cell proliferation and the generation of killer cells LAK is regulated by protein tyrosine kinase (PTK). In contrast, the generation of CD3-induced killer cells CD3-AK is primarily a PKC (protein kinase C)-dependent event. However, IL-4 can augment the cytolytic activity of CD3-AK cells and this augmentation effect is regulated by PTK. Our results indicate that both PTK and PKC play pivotal roles in the generation of different killer cells, depending on the signal transduction pathway. 2. The potential use of PKC inhibitors as a tool to study the biological functions of PKC isozymes. After nearly two decades of intensive study, the biological functions of most of the PKC isozymes still elude our understanding. Using different PKC inhibitors to study their effect on the alphaCD3-induced activated killer cells (CD3-AK), a PKC-dependent event, we found that there are both redundancy and diversity in PKC isozymes. Different isozymes may give the same effect in regulating a particular biological function, or they may oppose each other in the regulatory circuit. Our results demonstrate that PKC inhibitors can be used in the initial step to dissect out the functions of different PKC isozymes. 3. Cancer immunotherapy/gene therapy. In collaboration with Drs. W.K Yang and J. Peng of Academia Sinica, a joint project is established for cancer immuno-therapy/gene therapy. The first phase of work is to perform in vitro and in vivo studies in the animal models. Tumor cells are doubly trasduced with thymidine kinase and GM-CSF genes, their effect on the chemoimmunotherapy are evaluated in the syngeneic system.
