Targeting of saporin to CD25-positive normal and neoplastic lymphocytes by an anti-saporin/anti-CD25 bispecific monoclonal antibody: in vitro evaluation.
This study has been designed to verify the specific toxicity of saporin, a type 1 ribosome-inactivating protein (RIP), with the same activity as ricin A chain, targeted by a bispecific monoclonal antibody (bimAb) recognising both the CD25 antigen and the RIP. The CD25 antigen is expressed by lymphoid populations upon activation and by leukaemias and lymphomas with an activated membrane phenotype (Hodgkin's lymphoma, anaplastic large cell lymphoma, adult T cell leukaemia). The bimAb-saporin mixture was tested on CD25+ targets at different bimAb and saporin concentrations. Saporin, in the presence of a bimAb concentration of 10(-9) M, inhibited protein synthesis by CD25+ neoplastic lymphocytes (L540 and MT2 cell lines) with IC50S (concentrations giving 50% of inhibition) ranging from 8 x 10(-12) M to 3 x 10(-11) M. The saporin-bimAb mixture was also effective in blocking the phytohaemagglutinin-driven proliferation of normal lymphocytes, whereas it displayed the same level of toxicity exerted by saporin alone on an irrelevant CD25-negative cell line (EBV-infected B lymphoblastoid cell line). From these results it is possible to envisage a clinical use of this bimAb as a cytotoxic agent for CD25+ leukaemias and lymphomas, as well as an immunosuppressive agent for severe immune disorders such as graft-vs-host disease (GVHD) and transplanted organ rejection.
Istituto Nazionale per La Ricerca sul Cancro, Genova, Italy.
P L
PL
Tazzari
S
S
Zhang
Q
Q
Chen
S
S
Sforzini
A
A
Bolognesi
F
F
Stirpe
H
H
Xie
A
A
Moretta
S
S
Ferrini
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000972:Antineoplastic Agents, Phytogenic / Q000276:immunology / Q000494:pharmacology*; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology*; D015458:Leukemia, T-Cell / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009699:N-Glycosyl Hydrolases; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010835:Phytohemagglutinins / Q000494:pharmacology; D010940:Plant Proteins / Q000276:immunology / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D010940:Plant Proteins; D015375:Receptors, Interleukin-2; D054789:Ribosome Inactivating Proteins, Type 1; D014316:Tritium; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D013936:Thymidine