Our laboratory is trying to improve the therapeutic efficacy of tumor infiltrating lymphocytes (TIL) by generating populations of cells with improved specificity as well as modifying their in vivo localization to tumor. Current efforts on improving cell populations involve the use of immunization regimens with a variety of cytokine adjuvants and extracting and growing cells from immunization sites and draining lymph nodes. We are also studying the mediators of TIL motility in vitro using a Millipore migration system. Whole animal in vivo trafficking of tumorspecific TIL is being performed using a fluorescent cell surface dye with analysis of TIL content of organs by fluorescent cytometry. These studies are being correlated with ongoing clinical trials trafficking indium-labeled TIL. Furthermore, we are studying the adoptive transfer of genetically-modified T-cells in an attempt to establish the IL-2 and antigen requirements to promote proliferation of these populations and modulate their expression of gene products. This is being performed using a mouse T-cell line modified with the human TNF gene. Another project involves preclinical studies using a polyethylene glycol-modified form of IL-2, which has a prolonged circulating half-life. Murine models are used to examine the effect of PEG-IL-2 on adoptively-transferred cells. A Phase I trial using PEG-IL-2 has been conducted and a Phase III trial with IL-2 and PEG-IL-2 maintenance is underway.
