TIM-3 blockade enhances ex vivo stimulated allogeneic NK cell therapy for relapsed murine neuroblastoma after hematopoietic cell transplant.

Background: High-risk neuroblastoma (HR-NBL) is an aggressive tumor of the sympathetic nervous system with high risk of relapse and poor overall survival. Allogeneic hematopoietic cell transplant (allo-HCT) has been used previously in HR-NBL patients; however, graft-versus-host-disease (GVHD) and disease progression have limited clinical application. Ex-vivo stimulated allogeneic natural killer (NK) cells represent a potential approach to enhance the graft-versus-tumor (GVT) effect without exacerbation of GVHD but have not shown efficacy in NBL.

Feasibility and optimization ofF MRI on a clinical 3T with a large field-of-view torso coil.

The objective of this work is to: (1) demonstrate fluorine-19 (F) MRI on a 3T clinical system with a large field of view (FOV) multi-channel torso coil (2) demonstrate an example parameter selection optimization for aF agent to maximize the signal-to-noise ratio (SNR)-efficiency for spoiled gradient echo (SPGR), balanced steady-state free precession (bSSFP), and phase-cycled bSSFP (bSSFP-C), and (3) validate detection feasibility intissues.Measurements were conducted on a 3.0T Discovery MR750w MRI (GE Healthcare, USA) with an 8-channelH/F torso coil (MRI Tools, Germany).

CD155 blockade enhances allogeneic natural killer cell-mediated antitumor response against osteosarcoma.

Background: Allogeneic bone marrow transplant (alloBMT) is curative for hematologic malignancies through the graft-versus-tumor (GVT) effect but has been ineffective for solid tumors like osteosarcoma (OS). OS expresses CD155 which interacts strongly with inhibitory receptors TIGIT and CD96 but also binds to activating receptor DNAM-1 on natural killer (NK) cells. CD155 has never been targeted after alloBMT.

Combining Immunocytokine and Activated NK Cells as a Platform for Enhancing Graft-Versus-Tumor Effects Against GD2 Murine Neuroblastoma.

Management for high-risk neuroblastoma (NBL) has included autologous hematopoietic stem cell transplant (HSCT) and anti-GD2 immunotherapy, but survival remains around 50%. The aim of this study was to determine if allogeneic HSCT could serve as a platform for inducing a graft-versus-tumor (GVT) effect against NBL with combination immunocytokine and NK cells in a murine model. Lethally irradiated C57BL/6 (B6) x A/J recipients were transplanted with B6 bone marrow on Day +0.

Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors.

Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options.

CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1/2 and BCL2 inhibition through CNS infiltration.

Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival and proliferation of T-ALL . Using a xenograft model, the combination treatment fails to improve survival, with death from hind limb paralysis.

Programmed cell death protein 1 on natural killer cells: fact or fiction?

Programmed cell death protein 1 (PD-1) has become one of the most investigated targets for cancer immunotherapy. Most research has centered on inhibiting PD-1 on T cells, but there is increased interest in understanding the role of PD-1 on NK cells. While the expression of PD-1 on NK cells has been controversial, with papers publishing contradictory results in multiple models, there is increased clinical interest in NK and PD-1 immunotherapy.