What does this research mean for the field?

The developed technologies enable the rapid generation of diverse bispecific antibodies targeting CD28 and CD3, enhancing T cell-mediated tumor cell killing. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to develop multispecific antibodies targeting CD3 and CD28 to enhance T cell activation and cancer therapy.

February 20, 2026

Abstract C001: Rapid and efficient generation of format-diverse co-stimulatory CD28 and CD3 multispecific antibody panels for T cell engagement via complementary technologies

Key Points

The aim is to develop multispecific antibodies targeting CD3 and CD28 to enhance T cell activation and cancer therapy.
Identified co-stimulatory CD28 antibodies from synthetic IgG and HCAb libraries using a yeast-based platform.
Optimized affinity and developability of discovered antibodies to create a diverse panel.
Generated bispecific CD28 x HER2 antibodies employing various chain pairing technologies.
Assessed the ability of bispecific antibodies to stimulate T cell-dependent cytotoxicity.
Achieved over 95% desired pairing in bispecific antibody production using a single transfection system.
Developed a variety of anti-CD28 antibodies leading to potential bispecific functionalities.
Demonstrated enhanced tumor cell killing in RTCC assays with paired bispecific antibodies.

Abstract

Abstract Background: Currently approved monospecific antibody checkpoint inhibitors are often insufficiently effective for all patients and/or indications. Thus, investigators are interested in targeting multiple signaling pathways and/or cell types to enhance clinical outcomes, often in the form of multispecific antibody treatments (‘multispecifics’). Many of these multispecifics target the T cell as T cell engagers (TCEs), with the majority targeting CD3 and a tumor-associated antigen (TAA) to activate T cell-dependent cellular cytotoxicity. Co-stimulation by targeting CD28 or CD137 in addition to CD3 has recently shown promise. However, the large number of possible topologies and added complexity for manufacturing necessitate the development and application of a robust set of complementary technologies that facilitate generation and allow for functional screening of large multispecific panels. Methods: Co-stimulatory antibodies against CD28 were identified from synthetic IgG (kappa 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C001.

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