Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention

Abstract

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T-cells, natural killer cells, and genetically modified T-cell receptors, are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventative and therapeutic options for common RVIs, and appropriate infection control and preventative strategies.

Pattern-Recognition Receptors and Immunometabolic Reprogramming: What We Know and What to Explore

“…Hence, metabolically engineered CAR T cells or CAR macrophages with intact RLR signaling may prove better immunotherapeutic approaches for cancer with lower side effects. For example, patients undergoing CAR T-cell therapy are highly immunosuppressive and develop severe bacterial and viral (IAV) infections [ 277 , 278 ]. RLR activation in mice attenuates TLR-mediated Th1 cell and Th17 immune response, inducing death at sublethal bacterial infection by suppressing the transcription of the gene encoding the p40 subunit of interleukin 12 (IL-12b) [ 279 ].…”