Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL.

The development of clinically functional chimeric antigen receptor (CAR) T cell therapy is the culmination of multiple advances over the last three decades. Axicabtagene ciloleucel (formerly KTE-C19) is an anti-CD19 CAR T cell therapy in development for patients with refractory diffuse large B cell lymphoma (DLBCL), including transformed follicular lymphoma (TFL) and primary mediastinal B cell lymphoma (PMBCL). Axicabtagene ciloleucel is manufactured from patients' own peripheral blood mononuclear cells (PBMC) during which T cells are engineered to express a CAR that redirects them to recognize CD19-expressing cells.

Differential contribution of beta-adrenergic receptors expressed on radiosensitive versus radioresistant cells to protection against inflammation and mortality in murine endotoxemia.

The sympathetic nervous system modulates immune responses via the secretion of catecholamines and subsequent activation of adrenergic receptors (ARs), and systemic catecholamine levels increase markedly in the setting of endotoxemia and sepsis. Previous studies have demonstrated that stimulation of beta-ARs by pharmacological agonists attenuates the inflammatory response to LPS observed in vitro and can increase survival in animal models of endotoxemia and sepsis. However, the consequences of beta-AR activation by endogenous catecholamines have not been explored in these settings.

Leptin acts in the periphery to protect thymocytes from glucocorticoid-mediated apoptosis in the absence of weight loss.

Leptin is a member of the IL-6 cytokine family and is primarily produced by adipose tissue. At high enough concentration, leptin engages leptin receptors expressed in the hypothalamus that regulate a variety of functions, including induction of weight loss. Mice deficient in leptin (ob/ob) or leptin receptor (db/db) function exhibit thymic atrophy associated with a reduction in double-positive (DP) thymocytes.

Differential ex vivo nitric oxide production by acutely isolated neonatal and adult microglia.

Microglia are the macrophage population residing in the parenchyma of the central nervous system (CNS), and are thought to play critical roles in CNS development, homeostasis and defense against pathogens. Microglia are capable of rapidly responding to microbial pathogens through engagement of their Toll-like receptors (TLRs). We first compared the efficiency of these responses in primary microglia acutely isolated from adult and neonatal mice.

Transneuronal mapping of the CNS network controlling sympathetic outflow to the rat thymus.

The thymus is a primary immune organ that is essential for the development of functional T cells. The thymus receives sympathetic innervation, and thymocytes and thymic epithelial cells express functional adrenergic receptors. In this study, we employed retrograde, transneuronal virus tracing to identify the CNS cell groups that regulate sympathetic outflow to the thymus.

Resident microglia from adult mice are refractory to nitric oxide-inducing stimuli due to impaired NOS2 gene expression.

Microglia are the immunoregulatory cells of the central nervous system (CNS) and share many characteristics with resident macrophages in extracerebral tissues. Nitric oxide (NO) is secreted by macrophages following induction of the NO synthase gene NOS2 by stimuli elicited during a T-cell response and/or by microbial products. NO regulates both innate and adaptive immune responses, such as killing intracellular pathogens and inhibiting T-cell proliferation.

Developmental dissociation of T cells from B, NK, and myeloid cells revealed by MHC class II-specific chimeric immune receptors bearing TCR-zeta or FcR-gamma chain signaling domains.

The T-cell receptor zeta (TCR-zeta) and FcR-gamma chains play a critical role in mediating signal transduction. We have previously described HIV glycoprotein 120 (gp120)-specific chimeric immune receptors (CIRs) in which the extracellular domain of CD4 is linked to the signaling domain of zeta (CD4zeta) or gamma (CD4gamma). Such CIRs are efficiently expressed following retroviral transduction of mature T cells and specifically redirect effector functions toward HIV-infected targets.