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Immunotoxins containing saporin linked to different CD2 monoclonal antibodies: in vitro evaluation
Author(s) -
Tazzari Pier Luigi,
Bolognesi Andrea,
Totero Daniela,
Lemoli Roberto M.,
Fortuna Alessandra,
Conte Roberto,
Crumpton Michael J.,
Stirpe Fiorenzo
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb03258.x
Subject(s) - saporin , immunotoxin , ricin , monoclonal antibody , microbiology and biotechnology , ribosome inactivating protein , monoclonal , antibody , chemistry , biology , immunology , biochemistry , ribosome , rna , gene , toxin
In this study we describe immunotoxins prepared with different CD2 monoclonal antibodies (mAbs) and a ribosome‐inactivating protein, saporin. The CD2 immunotoxins were tested on different models. Anti‐CD2–saporin conjugates inhibited protein synthesis by a neoplastic CD2+ cell line (SKW‐3) and by an interleukin 2 dependent polyclonal CD2+ lymphoid cell culture (T lymphoblasts), with IC 50 s ranging from 10 ‐13 m to 10 ‐11 m (as saporin). Similar results were obtained with proliferation inhibition tests ( 3 H‐thymidine incorporation) on phytohaemagglutinin (PHA) driven lymphoid cultures and on mixed lymphocyte culture activated lymphocytes. Moreover a CD2–ricin A chain conjugate was less effective than an analogous immunotoxin containing the same CD2 mAb and saporin in inhibiting lymphocyte proliferation induced by PHA (IC 50 approximately 10 ‐9 m as ricin A chain versus 10 ‐12 m as saporin). The conjugates were not toxic on bone marrow stem cells. These results suggest that CD2–saporin immunotoxins could represent an effective tool for CD2+ lymphomas or leukaemias, and for T‐dependent immune disorders, such as transplanted organ rejection and graft‐versus‐host disease.