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, hollowfiber 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. The objective of the Phase I research is to build on this experience and develop process control mechanisms and specifications for instrumentation that fit 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. A LAK cell-specific instrument will be developed in Phase II. This instrument will meet the technological and economic needs of commercial application, yet enhance individual immune cell therapeutics.
Anticipated Results: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.National Cancer Institute
