Systemic tumor regression with synergy therapy: radiotherapy and CAR-T.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most poorly prognostic digestive tract malignancies. CLDN18.2 CAR-T therapy has recently shown promising clinical effects in PDAC.

Decitabine enhances targeting of AML cells by NY-ESO-1-specific TCR-T cells and promotes the maintenance of effector function and the memory phenotype.

NY-ESO-1 is a well-known cancer-testis antigen (CTA) with re-expression in numerous cancer types, but its expression is suppressed in myeloid leukemia cells. Patients with acute myeloid leukemia (AML) receiving decitabine (DAC) exhibit induced expression of NY-ESO-1 in blasts; thus, we investigated the effects of NY-ESO-1-specific TCR-engineered T (TCR-T) cells combined with DAC against AML. NY-ESO-1-specific TCR-T cells could efficiently eliminate AML cell lines (including U937, HL60, and Kasumi-1cells) and primary AML blasts in vitro by targeting the DAC-induced NY-ESO-1 expression.

Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges.

The cytogenetic abnormalities and molecular mutations involved in acute myeloid leukemia (AML) lead to unique treatment challenges. Although adoptive T-cell therapies (ACT) such as chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the treatment of leukemias, especially B-cell malignancies, the optimal target surface antigen has yet to be discovered for AML. Alternatively, T-cell receptor (TCR)-redirected T cells can target intracellular antigens presented by HLA molecules, allowing the exploration of a broader territory of new therapeutic targets.

Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

The formation of the RUNX1-RUNX1T1 fusion protein, resulting from the t(8;21) translocation, is considered to be one of the initiating events of t(8;21) acute myeloid leukemia (AML). However, the mechanisms of the oncogenic mechanism of RUNX1-RUNX1T1 remain unclear. In this study, we found that RUNX1-RUNX1T1 triggers the heterochromatic silencing of UBXN8 by recognizing the RUNX1-binding sites and recruiting chromatin-remodeling enzymes to the UBXN8 promoter region.

The Advances and Challenges of NK Cell-Based Cancer Immunotherapy.

Natural killer (NK) cells can be widely applied for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization or human leukocyte antigens-matching. Several NK-based therapeutic approaches have been attempted in clinical practice, but their efficacy is not sufficient to suppress tumor development mainly because of lacking specificity. To this end, the engineering of NK cells with T cell receptor along with CD3 subunits (TCR-NK) has been developed to increase the reactivity and recognition specificity of NK cells toward tumor cells.

High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells.

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT).

Differential Regulation of chTLR3 by Infectious Bursal Disease Viruses with Different Virulence In Vitro and In Vivo.

Toll-like receptor 3 (TLR3) is one of the TLRs whose ligand is double-stranded RNA (dsRNA). Infectious bursal disease virus (IBDV) is a dsRNA virus that could be recognized by TLR3. The purpose of this study was to determine the role of the virulence of IBDV on the expression of chicken TLR3 (chTLR3).