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

P. L. Tazzari, L. Polito, A. Bolognesi, M. P. Pistillo, P. Capanni, G. L. Palmisano, R. M. Lemoli, A. Curti, L. Biancone, G. Camussi, R. Conte, G. B. Ferrara, F. Stirpe

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4222-4229
Number of pages8
JournalJournal of Immunology
Volume167
Issue number8
Publication statusPublished - Oct 15 2001

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this