Antibody Industry Trends: June 2026 | Bispecific ADCs: Dual-Targeted Payload Deliveries From Concept to Clinical Testing
As part of our regular updates, we bring you the Monthly Recap this week, spotlighting what you need to know in June.
Introduction
Antibody-drug conjugates, or ADCs, have become an important class of targeted cancer therapeutics because they combine the binding specificity of antibodies with the cytotoxic potency of small-molecule payloads. A conventional ADC contains three core components: a monoclonal antibody, a chemical linker, and a cytotoxic drug. The antibody recognizes a tumor-associated antigen, the ADC is internalized by the target cell, and the payload is released intracellularly to induce cell death.
Bispecific antibody-drug conjugates, or BsADCs, combines the payload-delivery function of an ADC with the dual-recognition capacity of a bispecific antibody. Instead of binding one antigen or one epitope, the antibody component can be designed to recognize two different antigens, or two distinct epitopes on the same antigen. This added specificity may improve tumor selectivity, increase internalization, or broaden activity across heterogeneous tumors.
The BsADC design logic at a glance
Trend 1: BsADCs are being engineered to improve internalization and payload delivery
In BsADC development, a tumor antigen may be abundant on the cell surface, but if it does not internalize efficiently after antibody binding, it may be a poor ADC target. Since most ADC payloads must reach intracellular compartments before release, internalization is an important determinant of activity.
BsADCs address this problem through two main design strategies:
BsADC discovery also requires assessment of:
Trend 2: Dual targeting is being used to address tumor heterogeneity and target escape
Tumor heterogeneity is a challenge for ADCs, as antigen expression can differ between patients, between lesions, and among neighboring cells within the same tumor. If an ADC depends on a single antigen, tumor cells with low or absent expression may escape treatment.
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BsADCs are being investigated as one way to expand tumor coverage. Dual-antigen recognition may increase the fraction of tumor cells that can be engaged, while biparatopic targeting may increase avidity and internalization when antigen expression is present but variable. If optimal activity requires co-expression of both targets on the same cell, then the targetable population may actually become narrower.
One mechanism that may help is the bystander effect. With cleavable linkers and membrane-permeable payloads, cytotoxic payload released inside antigen-positive cells can diffuse into nearby tumor cells with lower or absent antigen expression. This is important for addressing heterogeneous tumors, although there is the need to balance efficacy against off-target toxicity from premature payload release.
This idea is especially relevant in difficult-to-treat solid tumors. For example, bsADCs have potential in pancreatic ductal adenocarcinoma (PDAC), a cancer characterized by dense stroma, poor drug penetration, and a highly immunosuppressive tumor microenvironment.
Trend 3: BsADC development in the lens of manufacturability and stability
There is growing recognition that BsADC success depends heavily on developability. For example, a recent study examined bioorthogonal click chemistry as a modular strategy for assembling bispecific antibody conjugates. The authors compared tetrazine-based inverse electron demand Diels-Alder reactions using either trans-cyclooctene or bicyclononyne handles. Both approaches generated bispecific constructs that retained antigen recognition by ELISA, while the BCN-tetrazine system was described as more robust and the TCO-tetrazine system showed stronger time-temperature dependence.
This type of work is relevant because BsADC programs often require rapid evaluation of multiple antibody formats, target pairs, and linker-payload combinations. Chemical assembly may help early-stage teams screen candidate designs before committing to more resource-intensive manufacturing routes.
Stability is also an important factor. Another study evaluated the photosensitivity of three BsADCs under different light sources. The authors found that fluorescent lamp exposure induced BsADC photodegradation and attributed this primarily to reactive oxygen species generated from the payload after photoexcitation. They also observed higher oxidation at conventional Fc methionine residues in BsADCs than in unconjugated parental bispecific antibodies. This finding shows that payload conjugation can change the structural and degradation behavior of a bispecific antibody.
Clinical Landscape: BsADCs Moving Toward Pivotal Testing
There are no BsADCs that have been approved by a global regulatory agency yet. Approximately 211 BsADCs are currently in development, representing 14% of 1,554 active ADCs. This report states that 84% of BsADCs remained in discovery or preclinical stages, while four candidates had reached Phase III development: izalontamab brengitecan, JSKN-003, TQB-2102, and maridebart cafraglitide. All four Phase III candidates are being developed for East Asian markets, with three being oncology-based.
Examples of BsADC clinical programs
Outlook
BsADCs are moving from a largely preclinical concept toward a clinically testable modality. They have the potential to treat not only cancer but also other diseases, positioning them as a future direction for ADC development.
Biointron ’s ADC conjugation platform, combined with antibody expression and engineering platform advantages, can provide you with a complete service process from antibody expression, conjugation to quality assessment, meeting the needs for screening, testing, and evaluation of ADC in preclinical settings.