Adoptive cellular immunotherapy has recently demonstrated enormous promise as a metastatic cancer treatment. Despite this promise, lymphokine activated killer (LAK) cell therapy has been severely limited by the prohibitive task of in vitro immune cell proliferation. Recently, hollow fiber mammalian cell culture instrumentation has been applied to LAK cell culture. This technology generated large numbers of cells that led to successful safety studies on human patients at the University of Minnesota. The objective of the proposed phase I research is to build on this experience and develop process control mechanisms and specifications for instrumentation that fits scale-up requirements of LAK cell cultures. The overall phase II goal is to develop a cost effective instrument that automates all culture methodology required by immune cell therapeutics. Automated large scale culture in hollow fiber bioreactors incorporates several computerized process control schemes that maintain cultures for several months. Phase I research will begin specific process control development needed to scale-up and optimize the LAK cell culture environment. The proposed research will lead to Phase II development of a LAK cell specific instrument. This instrument will meet technological and economic needs of commercial application, yet enhance individual immune cell therapeutics. Currently, widespread use and effective cancer treatment by LAK cell therapeutics is limited by the tedious task of generating sufficient cell numbers. This research will lead to development of an automated method for generating large numbers of LAK cells. Instrumentation specifically designed for this task will eliminate several problems associated with the current methodology. The result will be an affordable, space efficient instrument that clinical laboratories can use to enhance cellular immunotherapeutics.
