Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.

Background: Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy.

Methods: The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing.

POLE2 knockdown suppresses lymphoma progression via downregulating Wnt/β-catenin signaling pathway.

Lymphoma is the most common malignant tumor arising from immune system. Recently, DNA polymerase epsilon subunit 2 (POLE2) was identified to be a tumor promotor in a variety of malignant tumors. However, the biological role of POLE2 in lymphoma is still largely unclear.

Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma.

Background: T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer.

Methods: We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule.

Timing of Tocilizumab Administration Under the Guidance of IL-6 in CAR-T Therapy for R/R Acute Lymphoblastic Leukemia.

Unlabelled: Chimeric antigen receptor T (CAR-T) cells targeting CD19 have achieved great clinical responses in patients with relapsed or refractory (R/R) acute B lymphoblastic leukemia. However, severe adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome restrict it to further application. Tocilizumab is the corner stone for the treatment of severe CRS.

Case Report: ITP Treatment After CAR-T Cell Therapy in Patients With Multiple Myeloma.

Chimeric antigen receptor T (CAR-T) cell therapy is an attractive strategy for patients with relapsed or refractory hematological malignancies including multiple myeloma (MM). T cells are engineered to attack malignant cells that express tumor-associated antigens and better efficacy could be achieved. However, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity are still challenges for CAR-T cell therapy.

Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis.

Background: Recently, chimeric antigen receptor-modified (CAR) T cell therapy for hematological malignancies has shown clinical efficacy. Hundreds of clinical trials have been registered and lots of studies have shown hematologic toxic effects were very common. The main purpose of this review is to systematically analyze hematologic toxicity in hematologic malignancies treated with CAR-T cell therapy.

A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma.

Background: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations.

Methods: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo.

Early coagulation tests predict risk stratification and prognosis of COVID-19.

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) is hitting the world hard, but the relationship between coagulation disorders and COVID-19 is still not clear. This study aimed to explore whether early coagulation tests can predict risk stratification and prognosis. PubMed, Web of Science, Cochrane Library, and Scopus were searched electronically for relevant research studies published up to March 24, 2020, producing 24 articles for the final inclusion.

Diagnostic and Prognostic Value of Plasma Factor V Activity and Parameters in Thrombin Generation for Disseminated Intravascular Coagulation in Patients with Hematological Malignancies.

In this study, we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies. A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology, Union Hospital, between Apr. 2014 and Dec.

Retrospective Evaluation of New Chinese Diagnostic Scoring System for Disseminated Intravascular Coagulation.

Objectives: To retrospectively validate the new Chinese DIC scoring system (CDSS).

Methods: This study retrospectively collected the information of 619 patients (371 cases with non-hematologic malignancies, 248 cases with hematologic malignancies) who suspected of DIC in Wuhan Union Hospital during 2013-4 to 2014-6. We validated CDSS by comparing it with three leading scoring systems, from International Society on Thrombosis and Haemostasis (ISTH), Japanese Association for Acute Medicine (JAAM) and Japanese Ministry of Health and Welfare (JMHW), and evaluated its prognostic value by 28 days mortality, APACHE II and SOFA score.

Role of plasma high mobility group box-1 in disseminated intravascular coagulation with leukemia.

Introduction: High mobility group box 1(HMGB1) is a DNA-binding protein which can act as a proinflammatory cytokine when released by necrotic cells, monocytes or macrophages. It also plays a role in the coagulation activation and several tumors including leukemia. The objective of this study was to investigate the role of HMGB1 in the diagnosis of DIC with leukemia.