Mutated Flt3Lg Provides Reduced Flt3 Recycling Compared to Wild-Type Flt3Lg and Retains the Specificity of Flt3Lg-Based CAR T-Cell Targeting in AML Models.

The cells of acute myeloid leukemia are defined by clonal growth and heterogenous immunophenotypes. Chimeric antigen receptors (CARs) commonly recognize molecular targets by single-chain antibody fragments (scFvs) specific to a tumor-associated antigen. However, ScFvs may form aggregates, thus stimulating tonic CAR T-cell activation and reducing CAR T-cell functioning in vivo.

Natural Flt3Lg-Based Chimeric Antigen Receptor (Flt3-CAR) T Cells Successfully Target Flt3 on AML Cell Lines.

Relapsed/refractory acute myeloid leukemia (AML) cannot be cured with chemotherapy alone, as the blasts survive the treatment. Chimeric antigen receptor (CAR) approaches for AML are being actively developed. CARs promote immune reactions through recognition of the target molecular epitopes at the surface of cancer cells.

p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression.

Mutations in the gene and microenvironmentally driven activation of hypoxia-inducible factor-1 (HIF-1) typically occur in later stages of tumorigenesis. An ongoing challenge is the identification of molecular determinants of advanced cancer pathogenesis to design alternative last-line therapeutic options. Here, we report that p53 mutants influence the tumor microenvironment by cooperating with HIF-1 to promote cancer progression.

p73 Alternative Splicing: Exploring a Biological Role for the C-Terminal Isoforms.

p73 (encoded by TP73 gene) is a p53 related protein that functions as a transcriptional factor. Similarly to p53, following DNA damage, p73 is stabilized and activated and controls expression of target genes that are involved in the regulation of cycle arrest and apoptosis. However, great complexity to the function of this gene is given by the wide range of its non-tumor-related roles, which include neurological development, ciliogenesis and fertility.

A Novel Hybrid Promoter ARE-hTERT for Cancer Gene Therapy.

describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human gene promoter (hTERT) and the antioxidant response element (ARE) from the human gene promoter. The hybrid promoter retains the tumor specificity of the basal promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter.