|Antibody Name:||Anti-Tac (mouse anti-tac MAT)(IgG2a | k)|
Queen, C., Schneider, W.P., Selick, H.E., Payne, P.W., Landolfi, N.F., Duncan, J.F., Avdalovic, N.M., Levitt, M., Junghans, R.P. and Waldmann T.A. "A humanized antibody that binds to the interleukin 2 receptor."
Proc. Natl. Acad. Sci. USA (1989) 86: 10029-10033.
Schneider, W.P., Glaser, S.M., Kondas, J.A. and Hakimi, J. "The anti-idiotypic response by cynomolgus monkeys to humanized antitac is primarily directed to complementarity-determining regions H1, H2 and L3" J. Immunol. (1993) 150:3086-3090.
|Acceptor Antibody:||Human IgG1 | k|
|Antigen:||p55 chain of the human interleukin 2 receptor (IL-2R)|
|Laboratory:||Protein Design Labs, CA; Stanford Univ, CA; NCI, MD|
|Design:||Chose homologous framework for VH plus complementary VL and used computer model of mouse variable regions to suggest backmutations.|
|Frameworks:||VH human EU (Subgroup I) | VL human EU (Subgroup I)|
|CDRs:||All 6 from VH and VL, Kabat Definition.|
VH G27Y,S30T,M48I,R66K,V67A,G94R,E103W | VL M48I,S60A
Chosen to "either influence their (CDR) conformation or interact directly with antigen".
VH F89V,F91Y,G94R,E103W,Y104G,N105Q,G107T | VL M48I,I63S
Unusual residues in EU (mouse residues are more typically human!)
|Binding:||About 1/3 (3-fold lower) affinity of mouse antibody, determined by competition binding to membrane-bound p55 chain of IL-2R.|
|Expression:||mouse myeloma Sp2/0|
|Comment:||Binds to activated T-cells so different to OKT3 antibody which binds to the entire T-cell population. Clinically useful for immunosuppressive treatment. First example using a rational design for the reshaped antibody.|
|Clinical Indication:||Filed for approval in US and Canada by Roche for the prevention of kidney transplant rejection episodes under the name SMART Anti-Tac Antibody (Zenapax(R), dacliximab).|
|José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.|