English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the zaia usage as premium feature

ZAIA

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the access of premium content as premium feature

Premium Content

Zendy Tools

Zendy Open

Despite therapeutic advances in recent years, there are still unmet medical needs for patients with multiple myeloma (MM). Hence, new therapeutic strategies are needed. Using phage display for screening a large repertoire of single chain variable fragments (scFvs), we isolated several candidates that recognize a heavily sulfated MM-specific glycoform of the surface antigen syndecan-1 (CD138). One of the engineered scFv-Fc antibodies, named MM1, activated NK cells and induced antibody-dependent cellular cytotoxicity against MM cells. Analysis of the binding specificity by competitive binding assays with various glycan ligands identified N-sulfation of glucosamine units as essential for binding. Additionally, site-directed mutagenesis revealed that the amino acids arginine and histidine in the complementarily determining regions (CDRs) 2 and 3 of the heavy chain are important for binding. Based on this observation, a heavy-chain antibody, known as a nanobody, and a peptide mimicking the CDR loop sequences were designed. Both variants exhibited high affinity and specificity to MM cells as compared to blood lymphocytes. Specific killing of MM cells was achieved by conjugating the CDR2/3 mimic peptide to a pro-apoptotic peptide (KLAKLAK) 2. In a co-culture model, the fusion peptide killed MM cells, while leaving normal peripheral blood mononuclear cells unaffected. Collectively, the development of antibodies and peptides that detect tumor-specific glycoforms of therapeutic targets holds promise for improving targeted therapies and tumor imaging.

cancers

Antibody Surface Profiling Identifies Glycoforms in Multiple Myeloma as Targets for Immunotherapy: From Antibody Derivatives to Mimetic Peptides for Killing Tumor Cells