Antibody Fragment-Drug Conjugates (FDCs) are drug conjugates built from antibody fragments or Fc-derived domains—such as scFvs, minibodies, or modified Fc fragments—covalently linked to small-molecule drugs through defined linker chemistries. By removing the full-length IgG structure used in traditional ADCs, FDCs reduce molecular size while preserving binding or pharmacokinetic function.
This fragment-based design enables improved tissue penetration, tunable systemic exposure, and controlled drug loading, making FDCs a flexible platform for applications in oncology, antivirals, and beyond.
In oncology, FDCs built from antigen-binding fragments offer an alternative to full-length ADCs for solid tumors. GD2-targeted FDCs (see Figure 1) constructed from scFvs or minibodies with auristatin payloads (MMAE or MMAF) have demonstrated:
Figure 1. Schematic of scFv- and minibody-based FDC synthesis via cysteine reduction and thiol-maleimide conjugation to MMAE or MMAF.
The results from this study validate antibody fragment-drug conjugation as an effective strategy for improving selectivity and performance in solid tumor models.
Cidara Therapeutics' CD388 demonstrates how Fc-based fragment-drug conjugation can be used to modulate pharmacokinetics rather than target tumor antigens. CD388 links a small-molecule neuraminidase inhibitor to a human antibody Fc fragment using a click-chemistry PEG linker, creating a long-acting antiviral designed to prevent influenza A and B (see Figure 2).
Figure 2. Schematic of CD388 showing PEG-mediated conjugation of a neuraminidase inhibitor to a human IgG1 Fc fragment, enabling simultaneous engagement of multiple influenza neuraminidase targets.
In this construct, the Fc fragment functions as a drug carrier, leveraging FcRn-mediated recycling for extended circulation, while the PEG linker improves solubility and stability. CD388 highlights how PEGylated fragment-drug conjugates (FDCs) can transform short-lived small molecules into long-acting therapeutics.
As a worldwide leading supplier of ADC linkers & FDC linkers, BroadPharm offers a comprehensive range of bioconjugation linkers and services to support pharmaceutical & biotech research & development:
PEG Linkers for solubility and PK optimization: https://broadpharm.com/product-categories/peg-linkers
Cleavable Linkers for controlled intracellular drug release: https://broadpharm.com/product-categories/adc-linkers/cleavable-linkers
Non-Cleavable Linkers for maximum plasma stability: https://broadpharm.com/product-categories/adc-linkers
In summary, fragment-drug conjugates enable diverse therapeutic applications, ranging from tumor-targeted oncology therapies using antibody binding fragments to long-acting antivirals such as Fc-based conjugates like CD388, as well as other indications requiring controlled drug exposure. Through linker-driven design, FDCs offer a flexible platform for tailoring efficacy, pharmacokinetics, and safety across disease areas.
Döhrmann, S., Levin, J., Cole, J. N., Borchardt, A., Amundson, K., Almaguer, A., Abelovski, E., Grewal, R., Zuill, D., Dedeic, N., Hough, G., Fortier, J., Donatelli, J., Lam, T., Chen, Z. Y., Jiang, W., Haussener, T., Noncovich, A., Balkovec, J. M., Bensen, D. C., … Tari, L. W. (2025). Drug-Fc conjugate CD388 targets influenza virus neuraminidase and is broadly protective in mice. Nature microbiology, 10(4), 912-926. https://doi.org/10.1038/s41564-025-01955-3
Kalinovsky, D. V., Kholodenko, I. V., Kibardin, A. V., Doronin, I. I., Svirshchevskaya, E. V., Ryazantsev, D. Y., Konovalova, M. V., Rozov, F. N., Larin, S. S., Deyev, S. M., & Kholodenko, R. V. (2023). Minibody-Based and scFv-Based Antibody Fragment-Drug Conjugates Selectively Eliminate GD2-Positive Tumor Cells. International Journal of Molecular Sciences, 24(2), 1239. https://doi.org/10.3390/ijms24021239