Issue Archive

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

The risk of recurrent stroke in untreated sickle cell anemia (SCA) is high, necessitating chronic transfusion therapy where resources allow. To identify feasible alternative therapy for children with SCA in resource-limited areas, Abdullahi and colleagues undertook a randomized, double-blind trial of 2 fixed-dose regimens of hydroxyurea. In this Plenary Paper, the authors provide evidence that both low- and moderate-dose hydroxyurea regimens are effective for secondary stroke prevention when chronic transfusion therapy is not possible.

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.

Clonal hematopoiesis (CH) is a common, age-associated phenomenon where somatic mutations in hematopoietic stem and progenitor cells impart a selective advantage and expansion of mutant progeny in blood. Using a novel irradiation- and transplantation-free murine model of Tet2-mutant CH, Caiado et al demonstrate the importance of age-associated inflammation (“inflammaging”) in clonal outgrowth and define interleukin-1 signaling as a therapeutically targetable driver of clonal expansion.

Thomas et al present a whole-genome sequencing analysis of 230 pediatric and adult Burkitt lymphomas (BL) and compare these with data from 295 diffuse large B-cell lymphomas. The authors report that adult and pediatric BL share a common pathobiology with Epstein-Barr virus status, influencing the genetic and molecular profiles in both entities. BL may be divided into 3 genetic subgroups with distinct molecular underpinnings, spurring research to better define this rare disease.

Mutations in calreticulin (CALR), an endoplasmic reticulum chaperone, modify the protein’s C-terminus, leading to intracellular ligand-independent thrombopoietin receptor signaling and causing myeloproliferative neoplasms (MPNs). Mutant CALR is also found in a soluble form, but its significance is unknown. Pecquet et al revealed that soluble mutant CALR acts in a paracrine fashion to selectively enhance the growth of surrounding CALR-mutant hematopoietic cells. These novel insights suggest new therapeutic opportunities to target CALR-mutant MPNs.

Weibel-Palade bodies (WPB) are endothelial cell–specific secretory organelles that store the hemostatic protein von Willebrand factor, along with many inflammatory and angiogenic mediators; the regulation of release of this cargo is essential for normal hemostasis. El-Mansi et al uncovered new regulators of WPB exocytosis and cargo expulsion through a high-throughput dual loss-of-function screen. Their data identified p21-activated kinase 2 (PAK2)–mediated recruitment of cytoskeletal septin as a crucial step in WPB exocytosis, furthering our understanding of this important hemostatic process.