PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.

Background: The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers.

Engineering amino acid uptake or catabolism promotes CAR T-cell adaption to the tumor environment.

Cancer cells take up amino acids from the extracellular space to drive cell proliferation and viability. Similar mechanisms are applied by immune cells, resulting in the competition between conventional T cells, or indeed chimeric antigen receptor (CAR) T cells and tumor cells, for the limited availability of amino acids within the environment. We demonstrate that T cells can be re-engineered to express SLC7A5 or SLC7A11 transmembrane amino acid transporters alongside CARs.

A randomised evaluation of low-dose Ara-C plus pegylated recombinant arginase BCT-100 versus low dose Ara-C in older unfit patients with acute myeloid leukaemia: Results from the LI-1 trial.

The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low-dose cytarabine (LDAC) or venetoclax-based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role in AML pathophysiology.

Invariant NKT cells metabolically adapt to the acute myeloid leukaemia environment.

Acute myeloid leukaemia (AML) creates an immunosuppressive environment to conventional T cells through Arginase 2 (ARG2)-induced arginine depletion. We identify that AML blasts release the acute phase protein serum amyloid A (SAA), which acts in an autocrine manner to upregulate ARG2 expression and activity, and promote AML blast viability. Following in vitro cross-talk invariant natural killer T (iNKT) cells become activated, upregulate mitochondrial capacity, and release IFN-γ.

Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity.

Hematological and solid cancers catabolize the semiessential amino acid arginine to drive cell proliferation. However, the resulting low arginine microenvironment also impairs chimeric antigen receptor T cells (CAR-T) cell proliferation, limiting their efficacy in clinical trials against hematological and solid malignancies. T cells are susceptible to the low arginine microenvironment because of the low expression of the arginine resynthesis enzymes argininosuccinate synthase (ASS) and ornithine transcarbamylase (OTC).

MicroRNA Signature of Traumatic Brain Injury: From the Biomarker Discovery to the Point-of-Care.

Traumatic brain injury (TBI) is a serious problem that causes high morbidity and mortality around the world. Currently, no reliable biomarkers are used to assess the severity and predict the recovery. Many protein biomarkers were extensively studied for diagnosis and prognosis of different TBI severities such as S-100β, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), neurofilament light chain (NFL), cleaved tau protein (C-tau), and ubiquitin C-terminal hydrolase-L1 (UCH-L1).