Uptake of methotrexate linked to an anti-EL4-lymphoma antibody by EL4 cells.
To study the mechanism of tumor inhibition, the uptake of methotrexate (MTX) covalently linked to a rabbit IgG antibody against a tumor-associated antigen on the surface of mouse EL4 lymphoma cells (AELG) has been compared with the uptake of free MTX and of MTX covalently linked to normal rabbit IgG (NRG). When EL4 cells were incubated at 37 degrees C with 10 microM free MTX uptake leveled off after 30 min, at 30 pmol/mg protein. In contrast, uptake of both conjugates under these conditions continued throughout an observation period of 6 h. At 6 h the net uptake of MTX bound to AELG was 40 pmol/mg protein and that of MTX bound to NRG was 24 pmol/mg protein. These results show that both MTX-AELG and MTX-NRG conjugates are taken up by EL4 cells. The rate at which EL4 cells took up bound MTX was much slower than that of free MTX but, at 6 h, the net uptake of MTX-AELG exceeded that of the free drug.
D000818:Animals; D000912:Antibodies, Neoplasm / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology; D007167:Immunotherapy; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy; D008727:Methotrexate / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D011817:Rabbits
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D008727:Methotrexate