The Fab of an antibody comprises the heavy- and light-chain variable regions and their first constant domains. Conventional antibodies have two Fabs. Nanobodies are isolated VHH single variable domains and are not Fabs (1). Fabs are sometimes used for biophysical studies and have been explored for therapeutic applications.
Observations
- Antibody fragments such as Fabs are cleared from circulation more rapidly than full-length Abs (2).
- Recombinant Fab and related antibody fragments can be expressed in E. coli (3).
- Fabs can enter tumors rapidly, but rapid clearance can limit tumor exposure and retention. Extending Fab circulation through albumin binding increased tumor accumulation (4).
1.
Ketaren NE, Fridy PC, Malashkevich V, Sanyal T, Brillantes M, Thompson MK, et al. Unique mechanisms to increase structural stability and enhance antigen binding in nanobodies. Structure. 2025;33(4):677-690.e5. Available from: https://doi.org/10.1016/j.str.2025.01.019
2.
Pimm MV, Andrew SM, Baldwin RW. Blood and tissue kinetics of radiolabeled anti-CEA monoclonal antibody and F(ab)2 and Fab fragments in nude mice with human tumour xenografts: implications for tumour imaging and radioimmunotherapy. Nuclear Medicine Communications. 1989;10(8):585–94. Available from: https://doi.org/10.1097/00006231-198908010-00007
3.
Carter P, Kelley RF, Rodrigues ML, Snedecor B, Covarrubias M, Velligan MD, et al. High Level Escherichia coli Expression and Production of a Bivalent Humanized Antibody Fragment. Nature Biotechnology. 1992;10(2):163–7. Available from: https://doi.org/10.1038/nbt0292-163
4.
Dennis MS, Jin H, Dugger D, Yang R, McFarland L, Ogasawara A, et al. Imaging Tumors with an Albumin-Binding Fab, a Novel Tumor-Targeting Agent. Cancer Research. 2007;67(1):254–61. Available from: https://doi.org/10.1158/0008-5472.can-06-2531