Zhu, Z. and Carter, P.
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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.
|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).|
Version M22 with CDRs as above
VH F27Y T28S S30T S49A R71V N73K L78A
|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|
|José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.|