[Management of adverse events of CAR-T therapy].

Chimeric antigen receptor T cell (CAR-T) therapy has strong efficacy as well as characteristic complications. Although overshadowed by the glaring clinical picture of cytokine releasing syndrome and immune effector cell-associated neurotoxicity syndrome, there are many other side effects that are important to manage. In this article, CAR-T-specific adverse events will be reviewed based on the actual clinical experience.

Novel technologies for improving the safety and efficacy of CAR-T cell therapy.

Chimeric antigen receptor-T (CAR-T) cell therapy has shown significant therapeutic efficacy in the treatment of hematological B-cell malignancies. However, the efficacy of CAR-T cell therapy against solid tumors is limited due to the heterogeneity of tumor antigens and the immunosuppressive tumor microenvironment. Therefore, there is strong demand for novel technologies to improve the efficacy of CAR-T cell therapy. In addition, as CAR-T cells often cause severe side effects, systems to control the activity of CAR-T cells so as to avoid or lessen the occurrence and intensity of these side effects are needed. Here, we describe recently emerging approaches to enhance and/or regulate CAR-T cell functions. These approaches have led to the development of CAR-T therapies with improved efficacy and safety, which are expected to be clinically applied to a variety of cancer types in combination with other therapies, such as immune checkpoint inhibitors, chemotherapy, molecular targeted drugs, and radiation therapy.

The Cytokine Expression in Patients with Cardiac Complication after Immune Checkpoint Inhibitor Therapy.

We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.

Chemokines and chemokine receptors during COVID-19 infection.

Chemokines are crucial inflammatory mediators needed during an immune response to clear pathogens. However, their excessive release is the main cause of hyperinflammation. In the recent COVID-19 outbreak, chemokines may be the direct cause of acute respiratory disease syndrome, a major complication leading to death in about 40% of severe cases. Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection. Here, we review the role of chemokines and their receptors in COVID-19 pathogenesis to better understand the disease immunopathology which may aid in developing possible therapeutic targets for the infection.

[Efficacy and safety of CD19 chimeric antigen receptor T cells for the treatment of 22 patients with B-cell lymphoma].

Objective: To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×106/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions: CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.