SBIR-STTR Award

Adoptive cellular immunotherapy (CI), specifically lymphokine-activated killer (LAK) cells, has developed into a promising method for effective cancer therapy. Unfortunately, LAK cell therapy is limited by the labor-intensive task of generating large numbers of activated lymphocytes. Conventional cell-culture methods cause large-scale LAK cell production to be extremely labor intensive. As a result, routine clinical or therapeutic application is hampered by the magnitude of this task. Endotronics, Inc.'s, hollow-fiber-based technology has been shown to be an efficient large-scale approach to mass LAK cell production. This instrumentation was originally designed for long-term, large-scale mammalian cell culture and associated protein production. To gain widespread acceptance in the field of CI, a user-friendly, cost-effective system must be developed. Phase I research will study the use of a simpler, less costly hollow-fiber system for LAK cell growth. The design goals are to produce a cost-effective system that will expand 109 peripheral blood lymphocytes into full LAK cells in 14 days. Phase II development will integrate the Phase I information into a dedicated CI system that can be easily operated by clinical laboratory staff.

Anticipated Results:
CI is being performed in a limited number of research institutes. The production of active killer cells is a laborious task requiring the skills and facilities of a cell-culturing laboratory. Endotronics, Inc.'s, CI system is being designed to be run by personnel associated with any hematology or blood-banking laboratory. With the development of a system meeting these design goals, the number of sites performing CI will increase enormously.National Institute of Allergy And Infectious Diseases

Therapeutic promise offered by adoptive cellular immunotherapy has focused attention on automated large scale mammalian cell culture instrumentation. One reason for this attention is the enormous logistical difficulties associated with generating sufficient numbers of lymphokine activated killer (LAK) cells, by conventional static culture techniques. This resource has severely limited the application and further development of this new alternative therapy. This Phase II study proposes to examine in detail, the biology and methodology required to effectively cultivate therapeutic lymphoid cells in hollow fiber bioreactor (HFBRX)-based instrumentation. Specific metabolic and immunologic parameters will be defined to improve lymphocyte growth and lytic function in automated perfusion culture. Also, improved methodology )e.g., cell harvest) will be developed for the LAK specific HFBRX flowpath developed during the Phase I project. The proposed research will lead to privately funded Phase II commercialization of a clinical instrument.