UCHT1

Antibody Name: UCHT1
References: Zhu, Z. and Carter, P. "Identification of heavy chain residues in a humanized anti-CD3 antibody important for efficient antigen binding and T cell activation" J. Immunol. (1995) 155:1903-1910.
Shalaby, M.R., Shepard, H.M., Presta, L., Rodrigues, M.L., Beverly, P.C.L., Feldman, M. and Carter, P. "Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene." J. Exp. Med. (1992) 175:217-225.
Rodrigues, M.L., Shalaby, M.R., Werther, W., Presta, L. and Carter, P. "Engineering a humanized bispecific F(ab')2 fragment for improved binding to T cells" Int. J. Cancer (1992) suppl 7: 45-50.
Donor Antibody: mouse
Acceptor Antibody: Human bivalent, bispecific F(ab')2, chemically coupled with 4D5.
Antigen: human T cell surface marker, CD3
Laboratory: Genentech, CA; ICRF, UK; Charing Cross Sunley Research Centre, UK
Design: Modelled mouse variable regions to examine difference between mouse and consensus sequences.
Frameworks: Abundant human VH SGIII | VL kSGI
CDRs: All 6 VH and VL, Kabat Definition, except CDR-H2 D65G (mouse->human).
Backmutations: Version M22 with CDRs as above
VH F27Y T28S S30T S49A R71V N73K L78A
VL F71Y
Binding: Version M22 similar to v9 in binding to Jurkat cells.
Expression: Fab fragments in E. coli and full-length mAbs in adenovirus-transformed human embryonic kidney cell line 293.
Comment: Tested mutations T57S V63F in CDR-H2, and FR change I69L. Found that Ag binding efficiencies correlate to T cell proliferation but not cytotoxicity in vitro.
Clinical Indication: Cancers overexpressing p185HER2

explanation of symbols and abbreviations

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