Harnessing T Cells for Potent CD19 Tumor Cell Elimination: The Impact of the CD3 Recruit-Tandab AFM11

The abstract describes a study on a therapeutic antibody targeting CD19, which is expressed in B cell development and malignancies. The CD3 RECRUIT-TandAb AFM11 is a humanized bispecific tetravalent antibody that binds to both CD3 and CD19, aiming to leverage T cells' cytotoxic capabilities against non-Hodgkin lymphoma (NHL). The TandAb was engineered with humanized variable domains and its properties were assessed through in vitro assays and an in vivo murine model.

The results show that AFM11 is highly potent in lysing CD19+ tumor cells across various cell lines and primary B-CLL tumors, with EC50 values in the low to sub-picomolar range. It outperforms other bivalent formats and requires high affinity binding to CD19 and CD3 for effective T cell recruitment. Both CD8+ and CD4+ T cells are involved in cytotoxicity, with CD8+ cells being faster. AFM11 does not activate T cells without CD19+ targets, suggesting a safety feature, and can induce T cell activation and target lysis without harming antigen-negative cells.

In vivo studies reveal that AFM11 significantly inhibits tumor growth in a dose-dependent manner, with complete suppression at higher doses and substantial reduction even at lower doses. A single dose is comparable to multiple administrations. The conclusion highlights AFM11 as a potent and efficacious candidate for treating B cell malignancies with a favorable safety profile.