Antitumor effect of diphtheria toxin A-chain gene-containing cationic liposomes conjugated with monoclonal antibody directed to tumor-associated antigen of bovine leukemia cells.

Abstract

Monoclonal antibody c143 against tumor‐associated antigen (TAA) expressed on bovine leukemia cells was conjugated to cationic liposomes carrying a plasmid pLTR‐DT which contained a gene for diphtheria toxin A‐chain (DT‐A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) in the multicloning site of pUC‐18. The specificity and antitumor effects of the conjugates were examined in vitro and in vivo using TAA‐positive bovine B‐cell lymphoma line as the target tumor. In vitro studies with the TAA‐positive cell line indicated that luciferase genecontaining cationic liposomes associated with the c143 anti‐TAA monoclonal antibody caused about 2‐fold increase in luciferase activity compared with cationic liposomes having no antibody, and also that the c143‐conjugated cationic liposomes containing pLTR‐DT exerted selective growth‐inhibitory effects on the TAA‐positive B‐cell line. Three injections of pLTR‐DT‐containing cationic liposomes coupled with c143 into tumor‐bearing nude mice resulted in significant inhibition of the tumor growth. The antitumor potency of the c143‐conjugated cationic liposomes containing pLTR‐DT was far greater than that of normal mouse IgG‐coupled cationic liposomes containing pLTR‐DT as assessed in terms of tumor size. These results suggest that cationic liposomes bearing c143 are an efficient transfection reagent for BLV‐infected B‐cell lymphoma cells, and that the delivery of the pLTR‐DT gene into BLV‐infected B‐cells by the use of such liposomes may become a useful technique for gene therapy of bovine leukosis.