Exotoxin Conjugatest

lyzing the transfer of the ADP-ribosyl moiety of NAD to elongation factor 2 (13, 14). PE was linked to Mab lH10 F(ab')2 to form anti-cervical carcinoma immunotoxins. Mab 1H10 is a murine IgG3 monoclonal antibody which reacts with a carbohydrate epitope of a glycoconjugate expressed on the surface of several types of human carcinomas including human cervical tumors (15). Mab 1H10 reacts with several human tumor cell lines including CaSki and ME-180 cervical carcinoma, HT-29 and SW I116 colon carcinoma, and RT 4 bladder carcinoma cells (15). Mab 1Hl0 was also shown to recognize 40% of human cervical and colon cancer tissues as well as some bladder, ovarian, lung, and stomach carcinoma tissues (15). No binding of Mab lHl0 to any of the normal human tissues and cells tested was found. Samples tested included cervix, ovary, breast, liver, colon, bladder, kidney, spleen, endometrium, lung, thyroid, cerebrum, esophagus, RBC, and lymphocytes (15). In this report, we describe immunotoxins formed by linking Pseudomonus exotoxin to the F(ab')2 fragment of Mab 1H10 by disulfide as well as thioether bonds. We show that PE linked to Mab lH10 F(ab')z can specifically kill cervical carcinoma cells rn vitro. We also show that lHl0-PE can suppress the growth of solid cervical carcinoma tumors growing s.c. in nude mice when administered either i.p. or i.v.