Reactions Related to CAR-T Cell Therapy

Abstract

The application of chimeric antigen receptor (CAR) T-cell therapy as a tumor immunotherapy has received great interest in recent years. This therapeutic approach has been used to treat hematological malignancies solid tumors. However, it is associated with adverse reactions such as, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), off-target effects, anaphylaxis, infections associated with CAR-T-cell infusion (CTI), tumor lysis syndrome (TLS), B-cell dysplasia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) and coagulation disorders. These adverse reactions can be life-threatening, and thus they should be identified early and treated effectively. In this paper, we review the adverse reactions associated with CAR-T cells, the mechanisms driving such adverse reactions, and strategies to subvert them. This review will provide important reference data to guide clinical application of CAR-T cell therapy.

MUC1-C integrates type II interferon and chromatin remodeling pathways in immunosuppression of prostate cancer

“… 12 In contrast, MUC1-C is not shed from the surface of cancer cells and the MUC1-C extracellular domain thus represents another potential target for CAR T cells. 12 Nonetheless, treating solid tumors with CAR T cells has had limited success to date 71 and, based on the present results and those in TNBCs, 69 the effects of MUC1-C on suppression of the immune TME could represent a significant challenge for this field. In this regard, targeting the MUC1-C extracellular domain with antibody-drug conjugates 72 and the MUC1-C intracellular domain with the GO-203 inhibitor 12 provide alternative approaches for killing MUC1-C-expressing tumor cells and reversing the associated immunosuppressive TME 73 , 74 that could be used in combination with other immunotherapeutics.…”

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice

“…In summary, the incidence of CRS is reported to range from 25 to 80%, while for ICANS, from 50 to 70% [ 36 , 37 ]. These potentially life-threatening responses are associated, respectively, with targeted cell lysis and related electrolyte imbalance.…”

“…Our experience with vaccines to prevent SARS-CoV-2 infection at an international level shows that they have a highly favorable safety profile, with some rare fatal events, considering the vast number of people vaccinated worldwide in the post-marketing setting. It must be highlighted that the biopharmaceutical technology that led, in a very short time, to the development of COVID vaccines (i.e., mRNA vaccines) comes from cancer immunotherapy research [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Commonly detected toxic responses following cancer vaccine administration include myalgia, cough, chills, fever, pain at the injection site, asthenia, flu-like syndrome, and respiratory abnormalities [ 20 ,…”

“…Furthermore, each subclass of genetic therapy has inherent limitations. For example, oncolytic viruses can affect only viral antigens, limiting the effectiveness of OV therapy; the reaction and the immune response have significant individual variability, and a relevant problem is the rapid viral elimination of OVs from the organism [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. In addition, CAR-T therapy requires a very complex lymphodepletion process, implemented with chemotherapy before infusion; the consequent risk of serious adverse events such as cytokine release syndrome calls for immediate management and advanced clinical skills [ 72 ].…”

Current Immunotherapeutic Approaches for Malignant Gliomas

“…This leads to the immune escape of tumors owing to the loss of the targeted antigen. In addition, there are other obstacles to CAR-T cell therapy, including limitations of trafficking and infiltration into tumor tissue owing to the BBB, immunosuppressive tumor microenvironment, systemic inflammatory response such as cytokine release syndrome, and limitation of CAR T cell persistence [ 59 60 ].…”