Example of chemically linked Fabs: two Fab' fragments linked with a thioether, resulting in a F(ab')2. The molecule is bound to a tumour cell via the tumour antigen CD30 and to a macrophage via an Fc receptor.
In the late 1990s and early 2000s, clinical trials with chemically linked Fabs were conducted for the treatment of various types of cancer. Early results were promising, but the concept was dropped because of high production costs.
^Glennie, M. J.; McBride, H. M.; Worth, A. T.; Stevenson, G. T. (1987). "Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments". Journal of immunology (Baltimore, Md. : 1950)139 (7): 2367–2375. PMID2958547.
^ abBorchmann, P.; Schnell, R.; Fuss, I.; Manzke, O.; Davis, T.; Lewis, L. D.; Behnke, D.; Wickenhauser, C.; Schiller, P.; Diehl, V.; Engert, A. (2002). "Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma". Blood100 (9): 3101–3107. doi:10.1182/blood-2001-12-0295. PMID12384405.
^Link, B. K.; Kostelny, S. A.; Cole, M. S.; Fusselman, W. P.; Tso, J. Y.; Weiner, G. J. (1998). "Anti-CD3-based bispecific antibody designed for therapy of human B-cell malignancy can induce T-cell activation by antigen-dependent and antigen-independent mechanisms". International Journal of Cancer77 (2): 251. doi:10.1002/(SICI)1097-0215(19980717)77:2<251::AID-IJC14>3.0.CO;2-E.