Unlocking the Potential of DuoBody-CD3xCD30: A Promising Anti-Tumor Agent for CD30-Positive Hematologic Malignancies

CD3 bispecific antibodies have shown potential in treating blood cancers. The CD30 antigen is commonly found in certain cancers like Hodgkin lymphoma and anaplastic large cell lymphoma but is rarely present in normal tissues. Despite advances in treatment with drugs like brentuximab vedotin, not all patients respond well, and side effects can be severe. A new bispecific antibody, DuoBody-CD3xCD30 (GEN3017), has been developed to target CD30-expressing tumor cells.

This antibody is an engineered Fc-silenced IgG1 that combines elements of a CD3ε and a CD30 monoclonal antibody, designed to activate T-cells and induce cytotoxicity in tumor cells. In vitro and ex vivo tests showed that DuoBody-CD3xCD30 effectively triggered T-cell responses, leading to the destruction of CD30-positive tumor cells from various malignancies, including those of the hematologic system. The effectiveness was evident even at low concentrations, and the level of CD30 expression on the tumor cells was linked to the potency of the antibody's effect.

The study also found that the presence of soluble CD30 in cell culture did not hinder the antibody's ability to promote T-cell cytotoxicity. Interestingly, T-cell activation led to an increase in CD30 expression on healthy T cells, but this did not affect their viability when exposed to the bispecific antibody.

Further research is being conducted to understand the detailed mechanism of action and to characterize the functional activity of DuoBody-CD3xCD30 ex vivo. The findings so far indicate that this bispecific antibody could be a promising therapeutic option for the treatment of CD30-positive hematologic malignancies.