Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastase. In vitro and in vivo studies with Lewis lung carcinoma.
The present study was undertaken in order to evaluate the possibility of using anti-tumor antibodies as specific carriers of chemotherapeutic drugs to tumor metastases. Xenogeneic and syngeneic antisera were prepared against a metastasizing C57BL tumor, the Lewis lung carcinoma (3LL). The binding of absorbed xenogeneic and syngeneic anti-3LL sera or their Ig fractions to 3LL tumor cells was assayed by direct and indirect methods. Antisera prepared against tumor cells from a local growth reacted to a similar extent with those obtained from the lung metastases. Radioiodinated immunoglobulins from syngeneic antisera injected into mice bearing metastases localized preferentially in metastasis-bearing lungs as compared to several other organs tested. No such preferential uptake was observed either in mice bearing metastases injected with iodinated normal Ig or in normal mice injected with iodinated anti-3LL Ig. This relative accumulation in the metastasis-bearing lungs was observed 3-4 days after the inoculation, when the whole Ig fraction was used, whereas a specific antibody-enriched preparation localized as early as 24 h after injection. Daunomycin--anti-3LL-Ig conjugates were effective inhibitors of tumor cells from both local and the metastatic growths. They were more active than either the free drug or drug conjugates of normal Ig, in in vitro assays.
D000818:Animals; D000912:Antibodies, Neoplasm; D001666:Binding Sites, Antibody; D003630:Daunorubicin / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D007136:Immunoglobulins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D014185:Transplantation, Isogeneic
D000912:Antibodies, Neoplasm; D007136:Immunoglobulins; D003630:Daunorubicin