Ki-4(scFv)–ETA′, a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice

摘要: The human lymphocyte activation marker CD30 is highly overexpressed on Hodgkin/Reed–Sternberg cells and represents an ideal target for selective immunotherapy. We used the murine anti-CD30 hybridoma Ki-4 to construct a new recombinant immunotoxin (rIT) possible clinical use in patients with CD30+ lymphoma. Hybridoma V genes were polymerase chain reaction-amplified, assembled, cloned, expressed as mini-library display filamentous phage. Functional scFv obtained by selection of binding phage CD30-expressing Hodgkin lymphoma cell line L540cy was inserted into bacterial expression vector pBM1.1 fused deletion mutant Pseudomonas exotoxin A (ETA′). Periplasmically Ki-4(scFv)–ETA′ demonstrated specific activity against variety assessed different vitro assays. To evaluate vivo antitumor activity, severe combined immunodeficient mice challenged lines treated immunotoxin. blood distribution time t½ 19 minutes, its serum elimination 193 minutes. single intravenous injection 40 μg rIT 1 day after tumor inoculation rendered 90% free, extending mean survival more than 200 days compared 38.1 phosphate-buffered saline control group ( P  < .001). This promising candidate further evaluation or other CD30+malignancies.