PMID: 8581382Oct 1, 1995Paper

A humanized, bispecific immunoadhesin-antibody that retargets CD3+ effectors to kill HIV-1-infected cells

Journal of Hematotherapy
S M ChamowR P Junghans

Abstract

We have developed a humanized, bispecific immunoadhesin-antibody (BsIAb) that targets and kills HIV-infected cells. Comprised of CD4-IgG and humanized anti-CD3-IgG, this BsIAb is bifunctional. First, in targeting, it exploits the natural affinity of CD4 for gp120 to target the BsIAb to HIV-infected cells, and second, it recruits and activates, through its anti-CD3 moiety, cytotoxic T lymphocytes (CTL) to lyse target cells in a non-MHC restricted manner. To produce purified BsIAb from supernantants of transfected mammalian cells, we designed a three-step recovery scheme based on the structural elements of this heterotrimeric protein. The ability of purified BsIAb to specifically lyse HIV-infected target cells was demonstrated using CTL from two different sources: whole peripheral blood lymphocyte (PBL) fractions and pure CTL preparations. In contrast, a human anti-gp120 antibody mediated lysis of HIV-infected target cells only with PBL fractions and not with purified CTL. Moreover, lysis observed in the presence of the human anti-gp120 antibody was completely blocked in the presence of human serum (which competes for Fc gamma receptor binding), whereas BsIAb-mediated lysis of target cells was not affected. We measured the monova...Continue Reading

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Citations

Feb 27, 2001·Journal of Immunological Methods·P Carter
Feb 5, 2003·Advanced Drug Delivery Reviews·Ying Cao, Laura Lam
Sep 2, 1998·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·S K Vaswani, R G Hamilton
Nov 17, 1998·Bioconjugate Chemistry·Y Cao, M R Suresh

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