CMN-006(CoImmune)

Chimeric antigen receptor (CAR) T cell expansion and persistence represent key factors to achieve complete responses and prevent relapses. These features are typical of early memory T cells, which can be highly enriched through optimized manufacturing protocols. Here, we investigated the efficacy and safety profiles of CAR T cell products generated from preselected naive/stem memory T cells (TN/SCM), as compared with unselected T cells (TBULK). Notwithstanding their reduced effector signature in vitro, limiting CAR TN/SCM doses showed superior antitumor activity and the unique ability to counteract leukemia rechallenge in hematopoietic stem/precursor cell-humanized mice, featuring increased expansion rates and persistence together with an ameliorated exhaustion and memory phenotype. Most relevantly, CAR TN/SCM proved to be intrinsically less prone to inducing severe cytokine release syndrome, independently of the costimulatory endodomain employed. This safer profile was associated with milder T cell activation, which translated into reduced monocyte activation and cytokine release. These data suggest that CAR TN/SCM are endowed with a wider therapeutic index compared with CAR TBULK.

Recently, the improvement of gelatin-based films for usage in food packaging has attracted more attention owing to their non-toxicity, biodegradability, availability, and renewability. In the current study, the improved gelatin-based films were produced using covalent interaction through dialdehyde kappa-carrageenan (DAK-car) and thymol-loaded zein nanoparticle content. The influences of DAK-car into the matrix of gelatin films (GEL) on the structural, total soluble matter (TSM), moisture content (MC), and water vapor permeability (WVP), and mechanical properties were investigated. After the formation of covalent crosslinking amongst the amino groups of GEL and the dialdehyde groups of DAK-car with the blending ratio of 1:2 (GEL 4% w/v): (DAK-car 1% w/v), a remarkably (p < 0.05) reduction was saw in TSM, MC, and WVP of film. The tensile strength of this film (72.26 ± 0.3 MPa) was ~20-fold higher compared with pure GEL film. It should also be noted that the presence of zein nanoparticles (ZNPs) did not have a notably effect on improving the attributes of gelatin-based film. However, the presence of thymol in concentrations of 0.25 and 0.5 mg/mL showed acceptable antioxidant and antimicrobial activities. As a result, GEL/DAK-car with blending ratio of 1:2 containing thymol-loaded ZNPs films demonstrated the valuable potential for application in active food packaging.