CAR T-Cell Therapy in Large B-Cell Lymphoma

Abstract

Chimeric antigen receptor (CAR) T-cell therapy represents an exciting innovation in the treatment of cancer. With the approval of two revolutionary anti-CD19 CAR T-cell therapies (axicabtagene ciloleucel [Yescarta] and tisagenlecleucel [Kymriah]) for relapsed/refractory large B-cell lymphoma, health-care providers must consider how to prepare for the future of cancer care. While these therapies have been shown to provide clinical benefit to many patients, they are associated with a range of adverse events (AEs) that will need to be identified, assessed, and managed. Widespread education of health-care providers, patients, and caregivers will also be essential to ensure the success of this novel treatment. This supplement aims to provide practical information to the advanced practitioner on a number of considerations relating to the implementation and expansion of CAR T-cell therapy, including CAR T-cell biology and mechanism of action, how to identify, grade, and manage treatment-related AEs, as well as best practices for educating patients and caregivers about this type of therapy.

Adipocyte and lipid metabolism in cancer drug resistance

“…These drugs are often given to patients in combination with conventional chemotherapeutics (102)(103)(104). Another example is immunotherapy using the genetically propagated tumor antigen-recognizing lymphocytes (e.g., chimeric antigen receptor T [CAR T] cells) (105,106), immune checkpoint inhibitors (107)(108)(109), and immunocytokines. Tumor inflammatory and fibrotic compartments are also attractive targets for treating various cancers.…”

Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges

“…CAR-T cells can recognize proteins, sugar chains, and lipids on the cell surface without being restricted by MHCs and can therefore also deal with the cancer cells from which HLA has been lost [198,199]. In particular, CD19 is an exemplary target antigen in B cell leukemia and lymphoma [200,201]. However, in solid tumors, it is difficult to design CAR-T cells, because no surface antigens as specific as CD19 have been identified [202].…”

The Landscape of CAR-T Cell Clinical Trials against Solid Tumors—A Comprehensive Overview

“…CD19-specific CAR-T cells induced impressive clinical regressions of leukemias or lymphomas in several clinical trials [4][5][6]. This resulted in the approval by the FDA and EMA of Kymriah ® (Tisagenlecleucel, Basel, Switzerland), for the treatment of B-cell acute lymphoblastic leukemia (ALL), and Yescarta ® (Axicabtagen-Ciloleucel, Santa Monica, CA, USA), for the treatment of aggressive B-cell non-Hodgkin lymphoma [3].…”

“…Looking at the geographical distribution of the registered clinical trials, it is clear that most of these trials are performed in China (n = 99; 50.0%; Figure 1), followed by the USA (n = 85; 42.9%; Figure 1), and only very few trials are taking place in Europe, Australia, and the rest of Asia (all together responsible for n = 14; 7.1%; Figure 1). Data considering (1) targeted antigen, (2) targeted tumor, (3) CAR format, (4) transfer method of the CAR into the T cells, (5) additionally introduced qualities of the CAR-T cells, (6) number of cells applied, (7) patient pretreatment, (8) clinical outcome, (9) adverse events, and several other parameters are summarized in the following chapters. Additional information on e.g., clinical outcome of the trials and adverse events was gathered through literature search on pubmed.ncbi.nlm.nih.gov [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”