Immunoliposomes

The murine anticarcinoembryonic antigen (CEA) mAb 2C-8 has been conjugated to large multi-

10 132 133 10

lamellar liposomes containing B compounds. , The maximum number of B atoms attached

Liposome ^ Folate receptor

* Folate PEG

FIGURE 6.8 Proposed mechanism of intracellular boron delivery based on receptor-mediated tumor cell targeting. Liposomes loaded with a boron compound (A) are conjugated to a targeting ligand (e.g., folate, transferrin (TF), or anti-EGFR antibody). These bind to receptors on the cell surface (B), following which they are internalized by receptor mediated endocytosis (C) into the acidified endosomal/lysosomal compartment. The boron compound then is released (D) into the cytosol by liposomal degredation, endosome/lysosome disruption or liposome-endosome/lysome membrane fusion.

Liposome ^ Folate receptor

* Folate PEG

Boron compound

FIGURE 6.8 Proposed mechanism of intracellular boron delivery based on receptor-mediated tumor cell targeting. Liposomes loaded with a boron compound (A) are conjugated to a targeting ligand (e.g., folate, transferrin (TF), or anti-EGFR antibody). These bind to receptors on the cell surface (B), following which they are internalized by receptor mediated endocytosis (C) into the acidified endosomal/lysosomal compartment. The boron compound then is released (D) into the cytosol by liposomal degredation, endosome/lysosome disruption or liposome-endosome/lysome membrane fusion.

per molecule of mAb was approximately 1.2 X104. These immunoliposomes bound selectively to the human pancreatic carcinoma cell line, AsPC-1 that overexpressed CEA. Incubating the immunoliposomes with either MRKnu/nu-1 or AsPC-1 tumor cells, suppressed in vitro tumor cell growth following thermal neutron irradiation.134 This was dependent upon the liposomal concentration of the 10B-compound and on the number of molecules of mAb conjugated to the liposomes. Immu-noliposomes containing either (Et4N)2B10H10 and linked to the mAb MGb 2, directed against human gastric cancer135,136 or water-soluble boronated acridine (WSA, 11) linked to trastuzumab, directed against HER-2, have been prepared and evaluated in vitro.129 There was specific binding and high uptake of these immunoliposomes, which delivered a sufficient amount of 10B to produce a tumoricidal effect following thermal neutron irradiation.

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