CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process.

To enhance the potency of chimeric antigen receptor (CAR) engineered T cells in solid cancers, we designed a novel cell-based combination strategy with an additional therapeutic mode of action. CAR T cells are used as micropharmacies to produce a targeted pro-coagulatory fusion protein, truncated tissue factor (tTF)-NGR, which exerts pro-coagulatory activity and hypoxia upon relocalization to the vascular endothelial cells that invade tumor tissues. Delivery by CAR T cells aimed to induce locoregional tumor vascular infarction for combined immune-mediated and hypoxic tumor cell death.

HLA-G and HLA-E Immune Checkpoints Are Widely Expressed in Ewing Sarcoma but Have Limited Functional Impact on the Effector Functions of Antigen-Specific CAR T Cells.

Immune-inhibitory barriers in the tumor microenvironment of solid cancers counteract effective T cell therapies. Based on our finding that Ewing sarcomas (EwS) respond to chimeric antigen receptor (CAR) gene-modified effector cells through upregulation of human leukocyte antigen G (HLA-G), we hypothesized that nonclassical HLA molecules, HLA-G and HLA-E, contribute to immune escape of EwS. Here, we demonstrate that HLA-G isotype G1 expression on EwS cells does not directly impair cytolysis by G-specific CAR T cells (CART), whereas HLA-G1 on myeloid bystander cells reduces CART degranulation responses against EwS cells.

Group 13 metal complexes containing the bis-(4-methylbenzoxazol-2-yl)-methanide ligand.

To focus on the high importance of low-valent main group metal complexes, which can be applied to catalytic transformations, this article deals with the promising new ligand system (4-MeNCOC6H3)2CH2 (1). It is patterned on the well known nacnac ligand and further development of the parent bisheterocyclo methanes. In comparison with the results of previous studies based on the bisheterocyclo methanes (NCOC6H4)2CH2 and (NCOC6H4)2CH2 derivative 1 was modified by adding a methyl group to the annulated benzene perimeters to enhance the steric protection of a potentially coordinated main group metal cation.

Bis-(benzothiazol-2-yl)-amines and their metal amides: a structural comparison in the solid state.

Within this work, the field of amide ligand platforms for group 13 metal complexation, especially for Al(iii) is investigated in a synthetic as well as in a structural comparative approach. Starting from bis-heterocyclo methanides, which mimic the omnipresent nacnac ligand, the next enhancement in this class of ligands includes the exchange of the central methylene bridge by an amine nitrogen atom. With this modification three different sec.

An experimental study of the gas-phase reaction of the NO3 radical with alpha,beta-unsaturated carbonyl compounds.

The relative-rate technique has been used to obtain rate coefficients for the reaction between the NO3 radical and alpha,beta-unsaturated esters and ketones: methyl E-2-butenoate (k1), methyl 3-methyl-2-butenoate (k2), methyl E-2-methyl-2-butenoate (k3), 3-methyl-3-buten-2-one (k4), E-3-penten-2-one (ks), 4-methyl-3-penten-2-one (k6), and E-3-methyl-3-penten-2-one (k7). The rate constants obtained by the relative-rate method at T = 298 +/- 2 K and P = 760 +/- 5 Torr (N2 as bath gas) are: k1 = (1.85 +/- 0.