A novel affinity peptide technology (AJICAP) enables precise attachment of cancer-killing drugs to native antibodies without genetic engineering, producing effective antibody-drug conjugates that killed HER2-positive tumors in mice.
No antibody engineering neededAJICAP uses affinity peptides to direct site-specific drug conjugation on native, unmodified IgG antibodies — eliminating the need for genetic engineering that current ADC methods require.
What the researchers found
The AJICAP method used Fc-binding affinity peptide reagents to introduce thiol functional groups onto three specific lysine residues in native IgG antibodies — without any genetic engineering or antibody modification. A cytotoxic drug was then chemically linked to these thiol groups to create an antibody-drug conjugate.
The resulting HER2-targeting ADC demonstrated selective binding to HER2-positive cells (confirmed by surface plasmon resonance) and effectively killed HER2-positive tumors in an in vivo xenograft mouse model. The method provides site-specific drug attachment starting from any native antibody.
Why it matters
ADCs are one of the fastest-growing sectors in oncology drug development, but most require expensive and time-consuming antibody engineering to attach drugs at specific sites. AJICAP bypasses this by using peptides to direct drug attachment on native, unmodified antibodies. This could dramatically simplify and accelerate ADC development, potentially enabling any antibody to be converted into an ADC without genetic modification.
How the study worked
Fc affinity peptide reagents were designed to bind the Fc region of native IgG antibodies and introduce reactive thiol groups at three lysine positions. Cytotoxic drug molecules were conjugated via the thiol groups. Binding specificity was confirmed by surface plasmon resonance. Anticancer efficacy was tested in vitro against HER2-positive cells and in vivo using a xenograft mouse tumor model.
What this study cannot tell us
The study demonstrated proof-of-concept with a single HER2-targeting ADC. Drug-to-antibody ratio control and consistency across different antibody types were not extensively characterized. The long-term stability and pharmacokinetics of AJICAP-produced ADCs in comparison to engineered site-specific ADCs are not reported. Only one cytotoxic payload was tested. Manufacturing scalability and regulatory pathway considerations are not discussed.
How to read the evidence
This is a chemistry methodology paper with both in vitro binding validation and in vivo efficacy in a mouse xenograft model. The evidence for the method's functionality is strong, but no clinical data or comparative studies against established ADC platforms are available.
When this study was published
Published in 2019 in Angewandte Chemie, this technology has had several years to develop commercially. AJICAP has been licensed by Ajinomoto Bio-Pharma Services and is being used in ADC development programs.
The bigger picture
The ADC market has exploded, with drugs like trastuzumab deruxtecan (Enhertu) generating billions in sales. However, current site-specific conjugation methods typically require engineered cysteines, unnatural amino acids, or enzymatic modification. AJICAP represents a fundamentally different approach — using affinity peptides as molecular guides to direct drug attachment on native antibodies. Published in Angewandte Chemie (a top chemistry journal), this technology has the potential to democratize ADC production.
Questions still open
- How does the efficacy and safety profile of AJICAP-produced ADCs compare to site-specific engineered ADCs in head-to-head studies?
- Can the method be extended to any IgG antibody, or are some antibody frameworks incompatible with the Fc-binding peptide approach?
- What is the drug-to-antibody ratio consistency across batches, and does it meet the uniformity standards required for clinical ADC development?
Common questions
What is an antibody-drug conjugate and why does this technology matter?
How do the affinity peptides work in this system?
Read the original research
AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies.
Angewandte Chemie (International ed. in English), 58(17), 5592-5597
Citation
Yamada, Kei; Shikida, Natsuki; Shimbo, Kazutaka; Ito, Yuji; Khedri, Zahra; Matsuda, Yutaka; Mendelsohn, Brian A. (2019). AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies.. Angewandte Chemie (International ed. in English), 58(17), 5592-5597. https://doi.org/10.1002/anie.201814215