A bacutovirus-expressed chimeric recombinant IgG(1) (rlgG(1)) antibody, with C gamma(1) and C kappa human constant domains, was derived from the murine monoclonal antibody (mAb) 13B8.2, which is specific for the CDR3-like loop of the CID4 molecule and which inhibits HIV-1 replication. Chimeric rlgG1 antibody 13B8.2 blocked, in a dose-dependent manner, antigen presentation through inhibition of subsequent IL-2 secretion by stimulated T cells. The one-way mixed lymphocyte reaction was abrogated by previous addition of baculovirus-produced rlgG1 13B8.2 in the T-cell culture. Anti-proliferative activity of rlgG1 was demonstrated on CD3-activated CD4* T lymphocytes from healthy donors, such effect being associated with reduced IL-2 secretion of activated T cells. On the other hand, no proliferation inhibition was observed on CD4(+) T lymphocytes activated with phorbol ester plus ionomycin, suggesting that rlgG, 13B8.2 preferentially acts on a proximal TCR-induced signaling pathway. Treatment of DBA1/J human CD4-transgenic mice with 100 mu g of recombinant antibody for three consecutive days led to in vivo recovery of rlgG1 antibody 13B8.2 both coated on murine T lymphocytes and free in mouse serum, without CD4 depletion or down-modulation. These findings predict that the bacutovirusexpressed chimeric rlgG1 anti-CD4 antibody 13B8.2 is a promising candidate for immunotherapy. (c) 2005 Elsevier Inc. Alt rights reserved.
Biological activities on T lymphocytes of a baculovirus-expressed chimeric recombinant IgG(1) antibody with specificity for the CDR3-like loop on the D1 domain of the CD4 molecule
Troadec, S.; Bes, C.; Chentouf, M.; Nguyen, B.; Briant, L.; Jacquet, C.; Chebli, K.; Pugniere, M.; Roquet, F.; Cerutti, M.; Chardes, T.
2006-04 / vol 119 / pages 38-50
in-vivo; binding; t cell; hiv-1 infection; anti-cd4; anti-cd4 monoclonal-antibody; baculovirus; cell-activation; chimeric recombinant antibody; cross-linking; fc-gamma-riii; human igg1; immunotherapy; nonhuman-primates; signaling; transgenic mice