The goals of this research are to: (1) develop effective methods for controlled introduction of biologically active molecules (e.g., toxins, drugs, nucleic acids, enzymes, hormones, membrane antigens, and receptors) into cells; (2) use these methods to transfer membrane antigens or secreted cell products from one cell type to another as a means of comparing and clarifying various lymphocyte and macrophage receptor functions; (3) improve and make general an in vitro procedure for killing any cell subpopulation with antibody-toxin or -drug conjugates; and (4) identify network elements that regulate the expression of recurrent idiotypes. These goals rely in part on several methods we have developed for immunospecific attachment to selected cells of toxic agents or of membrane vesicles that may be loaded with particular molecules according to choice. With such targeted cells, we are investigating procedures for facilitating endocytosis of ligands and fusion with vesicles. Using polyethylene glycol or other fusagens, we can microinject the contents of liposomes into 20 to 80% of the cells in populations of lymphoid cell lines, normal B and T lymphocytes, and other cell types. With liposomes loaded with plasmid DNA, we can induce transfection of plasmacytomas and T lymphomas. Current research developments toward therapy involving antibody-directed agents and immunoregulation require better understanding of receptor function in the processing of membrane-bound complexes and in mediating cellular and idiotypic interactions. (LB)
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