Investigation on environmental factors contributing to bispecific antibody stability and the reversal of self-associated aggregates.

Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors-such as pH, buffer types, ionic strength, protein concentrations, and temperatures-on its stability and the reversal of its self-associated aggregates.

Effects of molecule hydrophobicity and structural flexibility of appended bispecific antibody on Protein A chromatography.

Appended bispecific antibody (aBsAb) with two single chain variable fragments (scFv) linked at the c-terminus of its heavy chains is one of the promising formats in bispecific therapeutics. The presence of hydrophobic and flexible scFv fragments render aBsAb molecules higher molecule hydrophobicity and structural flexibility compared to monoclonal antibody (mAb), thus making its purification more challenging. We set out to investigate how the unique molecular properties of aBsAb affect its performance on Protein A chromatography.

Comparative spatial proteomics of Plasmodium-infected erythrocytes.

Plasmodium parasites contribute to one of the highest global infectious disease burdens. To achieve this success, the parasite has evolved a range of specialized subcellular compartments to extensively remodel the host cell for its survival. The information to fully understand these compartments is likely hidden in the so far poorly characterized Plasmodium species spatial proteome.

Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies.

T-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenicity, effector functions, and pharmacokinetics. Here, we systematically compared T-bsAbs produced using eight different formats, evaluating the effect of molecular design of T-bsAbs on their manufacturability and functionality.

Strategies to enhance immunomodulatory properties and reduce heterogeneity in mesenchymal stromal cells during ex vivo expansion.

Therapies using mesenchymal stromal cells (MSCs) to treat immune and inflammatory conditions are now at an exciting stage of development, with many MSC-based products progressing to phase II and III clinical trials. However, a major bottleneck in the clinical translation of allogeneic MSC therapies is the variable immunomodulatory properties of MSC products due to differences in their tissue source, donor heterogeneity and processes involved in manufacturing and banking. This variable functionality of MSC products likely contributes to the substantial inconsistency observed in the clinical outcomes of phase III trials of MSC therapies; several trials have failed to reach the primary efficacy endpoint.

Rapid activation of distinct members of multigene families in Plasmodium spp.

The genomes of Plasmodium spp. encode a number of different multigene families that are thought to play a critical role for survival. However, with the exception of the P.

Immunomic Identification of Malaria Antigens Associated With Protection in Mice.

Efforts to develop vaccines against malaria represent a major research target. The observations that 1) sterile protection can be obtained when the host is exposed to live parasites and 2) the immunity against blood stage parasite is principally mediated by protective antibodies suggest that a protective vaccine is feasible. However, only a small number of proteins have been investigated so far and most of the proteome has yet to be explored.