Anti-Tac

Antibody Name: Anti-Tac (mouse anti-tac MAT)(IgG2a | k)
Reference: 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.
Donor Antibody: mouse
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.
Backmutations: 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).

explanation of symbols and abbreviations

José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.