Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19+ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19+ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose total body irradiation (LD-TBI) delivered to ALL-bearing mice prior to CAR T cell infusion considerably extended the overall survival benefit afforded by CAR T cells alone. Such an improved therapeutic activity was accompanied by a superior expansion of CAR T cells in vivo. These data encourage the initiation of clinical trials combining LD-TBI with CAR T cells in patients with hematological malignancies.
Inflammatory myopathies or myositides represent a group of severe skeletal muscle diseases characterized by muscle weakness, elevation of serum creatine kinase levels and muscle inflammatory cell infiltrates. Despite the contribution of a growing number of myositis-specific autoantibodies and the existence of characteristic dermatological features in dermatomyositis, the definitive diagnosis of myositis requires pathological examination of a muscle biopsy [1, 2]. To limit false negatives, this biopsy should be performed in an area of active disease [2]. In this context, magnetic resonance imaging (MRI) has gained interest since T1-weighted images are able to determine muscle damage such as atrophy, fatty infiltration and their distribution [3, 4] while T2-weighted images help to detect edema and thus may inform on the activity of the disease, i.e. muscle inflammatory infiltrates. This article is protected by copyright. All rights reserved.
Conclusion: Flash and conventional dose rate proton irradiation elicited a different hematological response, showing a larger impact of Flash irradiation. Additional (ongoing) studies are needed to investigate the parameters controlling the Flash effect and determine the differences between the irradiation cohorts. A full understanding of Flash proton effects is needed before clinical application.
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