Immunotoxins containing recombinant human-derived single-chain fragment variable (scFv) reagents (83 and 40) against CTLA-4 (CD152) linked to saporin, a ribosome-inactivating protein, were prepared and tested on CD3/CD28-activated T lymphocytes, MLRs, CTLA-4-positive cell lines, and hemopoietic precursors. Immunotoxins induced apoptosis in activated T lymphocytes and were able to specifically inhibit MLR between T lymphocytes and dendritic cells. The 83-saporin immunotoxin also inhibited the T cell activation in an MLR between T lymphocytes and an EBV-positive lymphoblastoid B cell line. Toxicity tests on hemopoietic precursors showed little or no effects in inhibiting colonies' growth. As the 83 scFv Ab was reactive also with activated mouse T lymphocytes, 83-saporin was tested in a model of tumor rejection consisting of C57BL/6 mice bearing a murine H.end endothelioma cell line, derived from DBA/2 mice. The lymphoid infiltration due to the presence of the tumor was reduced to a high extent, demonstrating that the immunotoxin was actually available and active in vivo. Thus, taking the results altogether, this study might represent a new breakthrough for immunotherapy, showing the possibility of targeting CTLA-4 to kill activated T cells, using conjugates containing scFv Abs and type 1 ribosome-inactivating protein.

Tazzari P.-L., Polito L., Bolognesi A., Pistillo M.-P., Capanni P., Palmisano G.L., et al. (2001). Immunotoxins containing recombinant anti-CTLA-4 single-chain fragment variable antibodies and saporin: In vitro results and in vivo effects in an acute rejection model. JOURNAL OF IMMUNOLOGY, 167(8), 4222-4229 [10.4049/jimmunol.167.8.4222].

Immunotoxins containing recombinant anti-CTLA-4 single-chain fragment variable antibodies and saporin: In vitro results and in vivo effects in an acute rejection model

Polito L.;Bolognesi A.
;
Lemoli R. M.;Curti A.;Conte R.;Stirpe F.
2001

Abstract

Immunotoxins containing recombinant human-derived single-chain fragment variable (scFv) reagents (83 and 40) against CTLA-4 (CD152) linked to saporin, a ribosome-inactivating protein, were prepared and tested on CD3/CD28-activated T lymphocytes, MLRs, CTLA-4-positive cell lines, and hemopoietic precursors. Immunotoxins induced apoptosis in activated T lymphocytes and were able to specifically inhibit MLR between T lymphocytes and dendritic cells. The 83-saporin immunotoxin also inhibited the T cell activation in an MLR between T lymphocytes and an EBV-positive lymphoblastoid B cell line. Toxicity tests on hemopoietic precursors showed little or no effects in inhibiting colonies' growth. As the 83 scFv Ab was reactive also with activated mouse T lymphocytes, 83-saporin was tested in a model of tumor rejection consisting of C57BL/6 mice bearing a murine H.end endothelioma cell line, derived from DBA/2 mice. The lymphoid infiltration due to the presence of the tumor was reduced to a high extent, demonstrating that the immunotoxin was actually available and active in vivo. Thus, taking the results altogether, this study might represent a new breakthrough for immunotherapy, showing the possibility of targeting CTLA-4 to kill activated T cells, using conjugates containing scFv Abs and type 1 ribosome-inactivating protein.
2001
Tazzari P.-L., Polito L., Bolognesi A., Pistillo M.-P., Capanni P., Palmisano G.L., et al. (2001). Immunotoxins containing recombinant anti-CTLA-4 single-chain fragment variable antibodies and saporin: In vitro results and in vivo effects in an acute rejection model. JOURNAL OF IMMUNOLOGY, 167(8), 4222-4229 [10.4049/jimmunol.167.8.4222].
Tazzari P.-L.; Polito L.; Bolognesi A.; Pistillo M.-P.; Capanni P.; Palmisano G.L.; Lemoli R.M.; Curti A.; Biancone L.; Camussi G.; Conte R.; Ferrara ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/959734
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