Efficient Tumor Elimination with Minimal Cytokine Release: The Promise of TNB-486 Bispecific Antibody

The CD19 protein, which is selectively present in B-cells, is a promising target for treating B-cell cancers. Various treatments targeting CD19 have been developed, such as monoclonal antibodies and antibody drug conjugates, including bispecific antibodies that redirect T-cells (T-BsAbs). CAR-T cells, another form of therapy, have also been approved for treating certain blood cancers. However, these T-cell redirecting therapies can lead to severe side effects, particularly neurotoxicity, due to excessive T-cell activation.

A new bispecific antibody, TNB-486, has been designed to combat CD19-positive tumors while minimizing the release of cytokines that are associated with toxicity. This was achieved by using TeneoSeek, a next-generation sequencing platform that identifies antigen-specific antibodies. The platform was used to create a high-affinity CD19 antibody and a library of CD3 antibodies, which showed a wide range of T cell activation potency in vitro.

The efficacy and safety profile of TNB-486 were evaluated in comparison to other bispecific antibodies. The methods used included affinity and stability measurements, T-cell activation assays, cytokine level assessments, and in vitro and in vivo tumor lysis tests. TNB-486 demonstrated high affinity for CD19, potent cytotoxicity, and minimal cytokine release, even at effective doses for tumor lysis. In animal models, it effectively eliminated CD19-positive tumors at low doses and showed no off-target effects.

Overall, TNB-486 has shown to be a potentially effective and safer alternative to existing T-cell redirecting therapies for lymphoma treatment, with a distinct advantage of reduced cytokine secretion and comparable tumor cell lysis capabilities.