Combinatorial immunotherapy of anti-MCAM CAR-modified expanded natural killer cells and NKTR-255 against neuroblastoma.

Pediatric patients with recurrent metastatic neuroblastoma (NB) have a dismal 5-year survival. Novel therapeutic approaches are urgently needed. The melanoma cell adhesion molecule (MCAM/CD146/MUC18) is expressed in a variety of pediatric solid tumors, including NB, and constitutes a novel target for immunotherapy.

Corrigendum: Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

[This corrects the article DOI: 10.3389/fimmu.2024.

Combinatorial macrophage induced innate immunotherapy against Ewing sarcoma: Turning "Two Keys" simultaneously.

Background: Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal.

Efficiently targeting neuroblastoma with the combination of anti-ROR1 CAR NK cells and N-803 and in NB xenografts.

The prognosis for children with recurrent and/or refractory neuroblastoma (NB) is dismal. The receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is highly expressed on the surface of NB cells, provides a potential target for novel immunotherapeutics. Anti-ROR1 chimeric antigen receptor engineered expanded peripheral blood natural killer (anti-ROR1 CAR exPBNK) cells represent this approach.

Therapy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma in Children, Adolescents, and Young Adults.

Despite excellent cure rates among children, adolescents, and young adults (CAYAs) with mature B-cell non-Hodgkin lymphomas (B-NHLs) treated with chemoimmunotherapy, CAYAs with relapsed/refractory B-NHL remain difficult to treat, with a dismal prognosis. Reinduction and subsequent therapeutic management are not standardized. The armamentarium of active agents against B-NHL, including antibody-drug conjugates, monoclonal antibodies, checkpoint inhibitors, T-cell engagers, CAR T cells, CAR-natural killer (CAR-NK) cells, and cell signaling inhibitors, continues to expand.

Neurocognitive outcome in children with sickle cell disease after myeloimmunoablative conditioning and haploidentical hematopoietic stem cell transplantation: a non-randomized clinical trial.

Background: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes.

Objectives: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time.

A humanized orthotopic mouse model for preclinical evaluation of immunotherapy in Ewing sarcoma.

The advent of novel cancer immunotherapy approaches is revolutionizing the treatment for cancer. Current small animal models for most cancers are syngeneic or genetically engineered mouse models or xenograft models based on immunodeficient mouse strains. These models have been limited in evaluating immunotherapy regimens due to the lack of functional human immune system.

Inflammation-mediated fibroblast activation and immune dysregulation in collagen VII-deficient skin.

Inflammation is known to play a critical role in all stages of tumorigenesis; however, less is known about how it predisposes the tissue microenvironment preceding tumor formation. Recessive dystrophic epidermolysis bullosa (RDEB), a skin-blistering disease secondary to mutations and associated with chronic wounding, inflammation, fibrosis, and cutaneous squamous cell carcinoma (cSCC), models this dynamic. Here, we used single-cell RNA sequencing (scRNAseq) to analyze gene expression patterns in skin cells from a mouse model of RDEB.

Risk Factors Associated with Survival Following Ganciclovir Prophylaxis through Day +100 in Cytomegalovirus At-Risk Pediatric Allogeneic Stem Cell Transplantation Recipients: Development of Cytomegalovirus Viremia Associated with Significantly Decreased 1-Year Survival.

Cytomegalovirus (CMV) reactivation is a major cause of morbidity and nonrelapse mortality (NRM) in pediatric allogeneic stem cell transplantation (alloSCT) recipients. Approximately 80% of CMV seropositive alloHCT recipients will experience CMV reactivation without prophylaxis. The impacts of ganciclovir prophylaxis and subsequent CMV viremia on 1-year survival and 1-year NRM are unknown.

Early Postnatal Expression of Tgfβ-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with white matter injury (WMI) and reduced neurogenesis. IVH commonly arises from the germinal matrix, a highly cellular, transient structure, where all precursor cells are born, proliferate, and migrate during brain development. IVH leads to reduced progenitor cell proliferation and maturation and contributes to WMI.

Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: Results of a modified Delphi panel.

Introduction: Tumor lysis syndrome (TLS), which occurs spontaneously or in response to anticancer treatment, results in the release of intracellular potassium, phosphorus, and nucleic acids into the bloodstream, which results in secondary clinical complications that may be fatal. Prior TLS guidelines do not take into consideration potent novel oncologic agents or contemporary treatment paradigms with increased risk of TLS. Thus, a modified Delphi panel of experts was convened to provide an update for TLS management guidelines based upon a combination of supporting literature and practice consensus.

Children's Oncology Group's 2023 blueprint for research: Cellular therapy and stem cell transplantation.

Since the publication of the last Cellular Therapy and Stem Cell Transplant blueprint in 2013, Children's Oncology Group cellular therapy-based trials advanced the field and created new standards of care across a wide spectrum of pediatric cancer diagnoses. Key findings include that tandem autologous transplant improved survival for patients with neuroblastoma and atypical teratoid/rhabdoid brain tumors, one umbilical cord blood (UCB) donor was safer than two UCB donors, killer immunoglobulin receptor (KIR) mismatched donors did not improve survival for pediatric acute myeloid leukemia when in vivo T-cell depletion is used, and the depth of remission as measured by next-generation sequencing-based minimal residual disease assessment pretransplant was the best predictor of relapse for acute lymphoblastic leukemia. Plans for the next decade include optimizing donor selection for transplants for acute leukemia/myelodysplastic syndrome, using novel engineered cellular therapies to target a wide array of malignancies, and developing better treatments for cellular therapy toxicities such as viral infections and graft-vs-host disease.

Diagnosis and management of mature B-cell lymphomas in children, adolescents, and young adults.

Mature B-cell lymphoma in children, adolescents and young adults comprises three major histological subtypes including in order of frequency Burkitt, germinal center diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma. The cure rate of the first two with aggressive short chemotherapy based on clinical grouping is ∼90% in resource rich countries. Recent data has shown that incorporation of immune therapy has enhanced event free survival in advanced patients.

Cellular and humoral immunotherapy in children, adolescents and young adults with non-Hodgkin lymphoma.

The prognosis is dismal (2-year overall survival less than 25%) for childhood, adolescent, and young adult (CAYA) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL). Novel targeted therapies are desperately needed for this poor-risk population. CD19, CD20, CD22, CD79a, CD38, CD30, LMP1 and LMP2 are attractive targets for immunotherapy in CAYA patients with R/R NHL.

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS).

Donor chimerism and immune reconstitution following haploidentical transplantation in sickle cell disease.

Introduction: We previously reported the initial results of a phase II multicenter transplant trial using haploidentical parental donors for children and aolescents with high-risk sickle cell disease achieving excellent survival with exceptionally low rates of graft-versus-host disease and resolution of sickle cell disease symptoms. To investigate human leukocyte antigen (HLA) sensitization, graft characteristics, donor chimerism, and immune reconstitution in these recipients.

Methods: CD34 cells were enriched using the CliniMACS system with a target dose of 10 x 10 CD34 cells/kg with a peripheral blood mononuclear cell (PBMNC) addback dose of 2x10 CD3/kg in the final product.

Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial.

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI.

Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations.

High grade gliomas are identified as malignant central nervous tumors that spread rapidly and have a universally poor prognosis. Historically high grade gliomas in the pediatric population have been treated similarly to adult high grade gliomas. For the first time, the most recent classification of central nervous system tumors by World Health Organization has divided adult from pediatric type diffuse high grade gliomas, underscoring the biologic differences between these tumors in different age groups.