Festival of Biologics, Basel, Switzerland
November 2, 2022
Background and novelty: Combinatorial selection strategies and advances in protein engineering have been successful in generating new therapies based on diverse large molecules. Bi- and multi-specific antibodies, antibody drug conjugates (ADCs), chimeric antigen receptors (CARs), engineered T-cell receptors (TCRs) and other formats offer new approaches to treatment. Highly engineered molecules also pose new challenges in their complex design, screening, and production, either as dedicated molecules or in the context of cell therapies (e.g., CAR-T cells). Efficient workflow infrastructure combining computational molecule design with powerful high-throughput (HT) screening system is vital for their research and development (R&D) at industrial scale.
Experimental approach: We have designed a combined R&D platform, which represents a highly structured database transforming the complexity of molecule design, HT screening, and production processes into organized workflow steps. Efficient molecule assembly mechanisms have been created to design large panels of novel biomolecules. Tools for pooled cloning deconvolution and chain pairing recovery have been implemented. The platform was designed to support screening of the best candidates and of the best-producer cell lines via built-in tools for developability assessment.
Results and discussion: We present concrete use cases supporting end-to-end large molecule and cell therapy R&D. Our special focus is on in silico molecule assembly, molecule format activity comparisons, developability assessments, and on the development and evaluation of therapeutic cell lines. The platform shows unmatched flexibility in handling and exploring novel therapeutic modalities and supports increased efficiency and speed in their design, screening, and development.