Cocktails of ricin a-chain immunotoxins against different antigens on hodgkin and sternberg-reed cells have superior anti-tumor effects against H-RS cells in vitro and solid Hodgkin tumors in mice

✍ Scribed by Andreas Engert; Claudia Gottstein; Heribert Bohlen; Ute Winkler; Gisela Schön; Oliver Manske; Roland Schnell; Volker Diehl; Philip Thorpe

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 645 KB
• Volume: 63
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910630226

✦ Synopsis

Three ricin A-chain immunotoxins (ITS) recognizing different antigens on Hodgkin-Reed/Sternberg (H-RS) cells were evaluated for their anti-tumor effects when used in combination as "cocktails". These ITS, 66 I0.dgA (CD25). HRS3.dgA (CD30). and IRac.dgA (70 kDa), strongly inhibited the growth of L54OCy H-RS cells in vitro. The protein synthesis of this cell line was reduced more efficiently by the combination of 2 of these ITS than by 66 I O.dgA, HRS3.dgA or IRac.dgA alone. A cocktail of all 3 ITS was most effective in vitro. This was at least in part due to the non-homogeneous distribution of CD25, CD30 or lRac on the L54OCy H-RS target cells and to the fact that subpopulations deficient in one antigen nevertheless expressed appreciable levels of the other target antigens. IT cocktails were also superior as anti-tumor agents in nude mice with solid L54OCy tumors. Ninety percent of mice treated with cocktails containing 2 or 3 ITS had continuous complete remissions (CCR), as compared with only 40% of mice treated with the same dose of a single IT. Analysis of 7 L54OCy sub-lines re-established ex vivo from mice that relapsed after having achieved complete remission (CR) after therapy with a single IT showed that the surviving tumor cells were antigen-deficient variants which were resistant to the original IT, but which could be killed by ITS directed against other target antigens. Thus, IT cocktails give superior results against human H-RS cells, both in vitro and in vivo.