p-IgGen: a paired antibody generative language model.

Summary: A key challenge in antibody drug discovery is designing novel sequences that are free from developability issues-such as aggregation, polyspecificity, poor expression, or low solubility. Here, we present p-IgGen, a protein language model for paired heavy-light chain antibody generation. The model generates diverse, antibody-like sequences with pairing properties found in natural antibodies.

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells.

Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3 T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models.

Toward enhancement of antibody thermostability and affinity by computational design in the absence of antigen.

Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within the field of biologics. tools that can streamline the process of antibody discovery and optimization are critical to support a pipeline that is growing more numerous and complex every year. High-quality structural information remains critical for the antibody optimization process, but antibody-antigen complex structures are often unavailable and antibody docking methods are still unreliable.