0000000000812813
AUTHOR
Klaus Kühlcke
Homodimeric murine interleukin-3 agonists indicate that ligand dimerization is important for high-affinity receptor complex formation.
Homodimeric murine interleukin 3 (mIL-3) agonists were generated by intermolecular cystine-bonding. Steady-state binding assays and association kinetics performed at 4 degrees C using these agonists revealed specific binding to both the high- and low-affinity receptor. DSS-mediated crosslinking studies performed at 4 degrees C with agonist concentrations compatible with high-affinity receptor complex formation allowed to detect protein complexes of the alpha chain, the beta chain(s) and the high-affinity receptor complex migrating with apparent molecular weights of 90 kDa, 140 kDa, and above 180 kDa, respectively. In contrast, monomeric mIL-3 was crosslinked to the alpha chain receptor only…
An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors.
A one-two, CAR-T cell punch Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard et al. describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They introduce the tight junction protein claudin 6 (CLDN6) as a new CAR-T cell target and designed a nanoparticulate RNA vaccine encoding a chimeric receptor directed toward CLDN6. This lipoplex RNA vaccine promotes CLDN6 expression on the surface of dendritic cells, which in turn stimulates and enhances the efficacy of CLDN6-CAR-T cells for improved tu…