Method for screening for an anti-CD4 antibody suitable for use in immunotherapy
A humanized antibody derived from mouse monoclonal anti-CD4 antibody B-F5 is able to activate CD25+CD4+ regulatory T cells and is useful for preparing immunosuppressive compositions.
1. A method for screening for an anti-CD4 antibody for use in immunotherapy, the method comprising:
(a) contacting a candidate anti-CD4 antibody with CD4+CD25+ regulatory T cells;
(b) assessing the ability of said candidate to activate said CD4+CD25+ regulatory T cells by conducting an effector T cell proliferation assay comprising an allogenic mixed lymphocyte reaction in which the CD4 + CD25 + regulatory T cells from step (a) are cocultured with allogenic CD4 + CD45RA+CD25− T cell in the presence of CD2-depleted peripheral blood mononuclear cells that are syngenic for the CD4 + CD25 + regulatory T cells; and
(c) identifying and selecting an anti-CD4 antibody which activates the CD4+CD25+ regulatory T cells to inhibit the proliferation of CD4 +CD45RA+CD25− T cells in step (b),
wherein the anti-CD4 antibody is a humanized version of an antibody comprising the complementarily-determining regions (CDRs) of SEQ ID NOs: 10 and 9, displayed in FIGS. 3 and 4 .
2. A method according to claim 1 further comprising:
(d) isolating the anti-CD4 antibody identified in step (c).
3. A method for producing a therapeutic composition comprising:
(a) selecting an antibody using the method of claim 1 ; and
(b) producing a therapeutic composition comprising the antibody.