[New perspectives in oncology: is selective destruction of tumor cells with immunotoxins in Hodgkin's disease an additional therapeutic alternative?].
In the present paper, the authors describe the production and testing of immunotoxins for clinical application in Hodgkin's disease. The immunotoxins were constructed by chemical coupling of deglycolysated ricin-A to monoclonal antibodies against antigens on Hodgkin's and Reed-Sternberg cells (CD25, CD30, IRac). The cytotoxic effect of the immunotoxins was investigated in vitro against Hodgkin's and Reed-Sternberg cells (H-RS) and in vivo against solid Hodgkin's tumors in nude mice and disseminated Hodgkin's tumors in SCID mice. Cross-reactivity with normal tissue and the staining behaviour observed in sections of Hodgkin's tissue of various subtypes proved important parameters for the assessment of clinical applicability. Of more than 30 evaluated MoAb's, eight immunotoxins were produced, of which six showed both, cytotoxic effects of considerable potency against Hodgkin's tumor cells and low cross-reactivity with vital human organs. The most effective immunotoxin, RFT5 gamma 1.dgA, (CD25) inhibits the growth of H-RS cells at concentrations of 7 pMol and destroys about 60% of solid Hodgkin's tumors of 0.5 cm in diameter in nude mice. This immunotoxin binds to virtually all tumor cells in more than 90% of patients with Hodgkin's disease. Sufficient quantities of RFT5 gamma 1.dgA were produced for the treatment of patients with refractory Hodgkin's disease. These patients are currently being treated in a phase I clinical trial.
Engert
A
A
Medizinische Universitätsklinik I Köln.
Gottstein
C
C
Winkler
U
U
Schön
G
G
Amlot
P
P
Thorpe
P
P
Diehl
V
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects*; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012276:Ricin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin
Neue Perspektiven in der Onkologie: Bietet die gezielte Zerstörung von Tumorzellen durch Immuntoxine beim Morbus Hodgkin eine zusätzliche therapeutische Alternative?