Our work is the development and evaluation of immunologic reagents in patients with malignancy. Preparation of single cell suspension from human tumors and evaluation and derivation of cloned and bulk populations of autologous lymphocytes reacting to them remain a major goal. Over 60 tumor preparations have been evaluated. Attempts to grown tumor reactive cells directly from tumors as well as lymph node samples is being evaluated. As part of the overall laboratory effort to evaluate lymphokine activated killer cells as a promising immunotherapeutic approach, we have been evaluating the long-term growth of these cells and have defined the precursor relationship to mature T cells. We have evaluated numerous culture conditions and believe that a moderate 10-100 fold expansion can be carried out and hope to apply this to patient protocols. Projects evaluating purification of the LAK precursor for use in binding studies as evaluated by flow microfluorimetry are being conducted 50-100 fold enrichment of LAK precursors has been obtained. Investigation of cellular interaction with tumor as well as LAK phenomenon, we've carried out an active program investigating the in vivo use of interleukin-2. Extensive studies with over 39 patients with both natural and recombinant IL-2 are being conducted as well as an extensive laboratory evaluation. These studies have defined a short half life of interleukin 2, profound immunologic effects with rapid regress of lymphokine activated killer precursor cells from the vascular compartment, development of Tac positive cells which appear to be leu 3+, 2-, indicating a possible expansion of helper cells as well as the demonstration of soluble IL-2 receptors in the serum of patients receiving IL-2. Future efforts will be designed to evaluate the role of IL-2 alone in an adjuvant setting in stage 2 melanoma as well as a continued evaluation of its use in the treatment of primary peritoneal tumors.
