54 results match your criteria Immunotherapeutic Targeting in Children


CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies.

Front Immunol 2022 4;13:867154. Epub 2022 May 4.

Department of Paediatric Haematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Read More

View Article and Full-Text PDF

Anti-CCR9 Chimeric Antigen Receptor T cells for T Cell Acute Lymphoblastic Leukemia.

Blood 2022 May 4. Epub 2022 May 4.

University College London Great Ormond Street Institute of Child Health, United Kingdom.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure in comparison to B-ALL. The potent immunotherapeutic approaches applied in B-ALL, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T cell aplasia is highly toxic. Read More

View Article and Full-Text PDF

Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity.

MedComm (2020) 2022 Jun 21;3(2):e137. Epub 2022 Apr 21.

Department of Hepatobiliary Surgery Weifang People's Hospital Shandong P. R. China.

CD4CD25 regulatory T cells (Tregs), a subpopulation of naturally CD4 T cells that characteristically express transcription factor Forkhead box P3 (FOXP3), play a pivotal role in the maintenance of immune homeostasis and the prevention of autoimmunity. With the development of biological technology, the understanding of plasticity and stability of Tregs has been further developed. Recent studies have suggested that human Tregs are functionally and phenotypically diverse. Read More

View Article and Full-Text PDF

Advancement of cancer immunotherapy using nanoparticles-based nanomedicine.

Semin Cancer Biol 2022 Apr 1. Epub 2022 Apr 1.

Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali 140306, Punjab, India. Electronic address:

Cancer has complex pathophysiology and is one of the primary causes of death and morbidity across the world. Chemotherapy, targeted therapy, radiation therapy, and immunotherapy are examples of traditional cancer treatments. However, these conventional treatment regimens have many drawbacks, such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance, leading to less potent/ineffective cancer treatment. Read More

View Article and Full-Text PDF

Exosomal microRNAs induce tumor-associated macrophages via PPARγ during tumor progression in SHH medulloblastoma.

Cancer Lett 2022 06 15;535:215630. Epub 2022 Mar 15.

Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing, 100191, China; Beijing Key Laboratory of Research and Transformation of Biomarkers for Neurodegenerative Diseases, Peking University Third Hospital, Peking University Health Science Center, Beijing, 100191, China. Electronic address:

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is composed of at least four molecular subgroups with distinct clinical characteristics. The sonic hedgehog (SHH) subgroup exhibits the most abundant tumor-associated microglia/macrophages (TAMs) infiltration. SHH-MB patients treated by anti-SHH drugs showed high drug resistance. Read More

View Article and Full-Text PDF

Immunotherapeutic Targeting of Mesothelin Positive Pediatric AML Using Bispecific T Cell Engaging Antibodies.

Cancers (Basel) 2021 Nov 26;13(23). Epub 2021 Nov 26.

Nemours Centers for Childhood Cancer Research & Cancer and Blood Disorders, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA.

Advances in the treatment of pediatric AML have been modest over the past four decades. Despite maximally intensive therapy, approximately 40% of patients will relapse. Novel targeted therapies are needed to improve outcomes. Read More

View Article and Full-Text PDF
November 2021

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

Cell Rep 2021 11;37(8):110047

University of Toronto Musculoskeletal Oncology Unit, Sinai Health System; Department of Surgery, University of Toronto, Toronto, ON, Canada.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. Read More

View Article and Full-Text PDF
November 2021

The landscape of coding RNA editing events in pediatric cancer.

BMC Cancer 2021 Nov 17;21(1):1233. Epub 2021 Nov 17.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Background: RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers.

Methods: Using RNA-Seq data mapped by a pipeline designed to minimize mapping ambiguity, we investigated RNA editing in 711 pediatric cancers from the St. Read More

View Article and Full-Text PDF
November 2021

Phenotypic plasticity of myeloid cells in glioblastoma development, progression, and therapeutics.

Oncogene 2021 10 23;40(42):6059-6070. Epub 2021 Sep 23.

Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second Hospital and Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P. R. China.

Glioblastoma (GBM) is the most common and malignant type of intracranial tumors with poor prognosis. Accumulating evidence suggests that phenotypic alterations of infiltrating myeloid cells in the tumor microenvironment are important for GBM progression. Conventional tumor immunotherapy commonly targets T-cells, while innate immunity as a therapeutic target is an emerging field. Read More

View Article and Full-Text PDF
October 2021

Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design.

J Immunother Cancer 2021 09;9(9)

Division of Hematology/Oncology/BMT, Children's Hospital Colorado, Aurora, Colorado, USA.

Background: Successful development of chimeric antigen receptor (CAR) T cell immunotherapy for children and adults with relapsed/refractory acute myeloid leukemia (AML) is highly desired given their poor clinical prognosis and frequent inability to achieve cure with conventional chemotherapy. Initial experiences with CD19 CAR T cell immunotherapy for patients with B-cell malignancies highlighted the critical impact of intracellular costimulatory domain selection (CD28 vs 4-1BB (CD137)) on CAR T cell expansion and in vivo persistence that may impact clinical outcomes. However, the impact of costimulatory domains on the efficacy of myeloid antigen-directed CAR T cell immunotherapy remains unknown. Read More

View Article and Full-Text PDF
September 2021

Targeting pediatric leukemia-propagating cells with anti-CD200 antibody therapy.

Blood Adv 2021 09;5(18):3694-3708

Bristol Institute for Transfusion Sciences, National Health Service Blood and Transplant Filton, Bristol, United Kingdom.

Treating refractory pediatric acute lymphoblastic leukemia (ALL) remains a challenge despite impressive remission rates (>90%) achieved in the last decade. The use of innovative immunotherapeutic approaches such as anti-CD19 chimeric antigen receptor T cells does not ensure durable remissions, because leukemia-propagating cells (LPCs) that lack expression of CD19 can cause relapse, which signifies the need to identify new markers of ALL. Here we investigated expression of CD58, CD97, and CD200, which were previously shown to be overexpressed in B-cell precursor ALL (BCP-ALL) in CD34+/CD19+, CD34+/CD19-, CD34-/CD19+, and CD34-/CD19- LPCs, to assess their potential as therapeutic targets. Read More

View Article and Full-Text PDF
September 2021

LTX-315-enabled, radiotherapy-boosted immunotherapeutic control of breast cancer by NK cells.

Oncoimmunology 2021 10;10(1):1962592. Epub 2021 Aug 10.

Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.

LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumor-targeting immune responses. Here, we investigated the therapeutic activity and immunological correlates of intratumoral LTX-315 administration in three syngeneic mouse models of breast carcinoma, with a focus on the identification of possible combinatorial partners. Read More

View Article and Full-Text PDF
October 2021

Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia.

Clin Cancer Res 2021 10 11;27(20):5718-5730. Epub 2021 Aug 11.

Fred Hutchinson Cancer Research Center, Seattle, Washington.

Purpose: We previously identified mesothelin (MSLN) as highly expressed in a significant fraction of acute myeloid leukemia (AML) but entirely silent in normal hematopoiesis, providing a promising antigen for immunotherapeutic targeting that avoids hematopoietic toxicity. Given that T cells genetically modified to express chimeric antigen receptors (CAR) are effective at eradicating relapsed/refractory acute lymphocytic leukemia, we developed MSLN-directed CAR T cells for preclinical evaluation in AML.

Experimental Design: The variable light (VL) and heavy (VH) sequences from the MSLN-targeting SS1P immunotoxin were used to construct the single-chain variable fragment of the standard CAR containing 41-BB costimulatory and CD3Zeta stimulatory domains. Read More

View Article and Full-Text PDF
October 2021

A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope.

Cell Rep Med 2021 07 21;2(7):100344. Epub 2021 Jul 21.

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Glypican 2 (GPC2) is a MYCN-regulated, differentially expressed cell-surface oncoprotein and target for immune-based therapies in neuroblastoma. Here, we build on GPC2's immunotherapeutic attributes by finding that it is also a highly expressed, MYCN-driven oncoprotein on small-cell lung cancers (SCLCs), with significantly enriched expression in both the SCLC and neuroblastoma stem cell compartment.By solving the crystal structure of the D3-GPC2-Fab/GPC2 complex at 3. Read More

View Article and Full-Text PDF

The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy.

Cancers (Basel) 2021 Jul 18;13(14). Epub 2021 Jul 18.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Read More

View Article and Full-Text PDF

Engineering of CD19 Antibodies: A CD19-TRAIL Fusion Construct Specifically Induces Apoptosis in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells In Vivo.

J Clin Med 2021 Jun 15;10(12). Epub 2021 Jun 15.

ALL-BFM Study Group, Department of Pediatrics I, Christian-Albrechts University Kiel and University Medical Center Schleswig-Holstein, Arnold-Heller Str. 3, Haus C, 24105 Kiel, Germany.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent malignancy in children and also occurs in adulthood. Despite high cure rates, BCP-ALL chemotherapy can be highly toxic. This type of toxicity can most likely be reduced by antibody-based immunotherapy targeting the CD19 antigen which is commonly expressed on BCP-ALL cells. Read More

View Article and Full-Text PDF

Advances in immunotherapeutic targets for childhood cancers: A focus on glypican-2 and B7-H3.

Pharmacol Ther 2021 07 14;223:107892. Epub 2021 May 14.

Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Cancer immunotherapies have revolutionized how we can treat adult malignancies and are being translated to pediatric oncology. Chimeric antigen receptor T-cell therapy and bispecific antibodies targeting CD19 have shown success for the treatment of pediatric patients with B-cell acute lymphoblastic leukemia. Anti-GD2 monoclonal antibody has demonstrated efficacy in neuroblastoma. Read More

View Article and Full-Text PDF

Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting.

Oncoimmunology 2021 02 4;10(1):1877459. Epub 2021 Feb 4.

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Rhabdomyosarcoma (RMS) is a heterogeneous soft tissue neoplasm most frequently found in children and adolescents. As the prognosis for recurrent and metastatic RMS remains poor, immunotherapies are hoped to improve quality of life and survival. CD137 is a member of tumor necrosis factor receptor family and a T cell costimulatory molecule which induces potent cellular immune responses that are able to eliminate malignant cells. Read More

View Article and Full-Text PDF
February 2021

Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma.

J Cell Immunol 2021 ;3(5):305-316

Oncogenomics Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.

Pediatric neuroblastoma is a heterogenous disease that accounts for significant morbidity and mortality in children. Deep genomic and transcriptomic profiling of patient tumors has revealed a low mutational burden and a paucity of therapeutic targets. Furthermore, different molecular subtypes, such as amplification, have been associated with adverse outcomes. Read More

View Article and Full-Text PDF
January 2021

Targeting Nuclear Receptors for Cancer Therapy: Premises, Promises, and Challenges.

Trends Cancer 2021 06 16;7(6):541-556. Epub 2020 Dec 16.

Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China. Electronic address:

Nuclear receptors are a family of transcription factors localized in cell nuclei, sensing specific ligands and fine-tuning a variety of cell physiological events. They have been intensively investigated in cancer biology. With their excellent properties of druggability and actionability, nuclear receptors have demonstrated much promise as novel therapeutic targets for different cancer types. Read More

View Article and Full-Text PDF

Immunotherapy approaches targeting neuroblastoma.

Curr Opin Pediatr 2021 02;33(1):19-25

Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Purpose Of Review: In the era of immune-oncology, a breakthrough in the field of pediatric solid tumor research has been the demonstration that immunotherapy for patients with high-risk neuroblastoma improves the event-free and overall survival. Immunotherapeutic approaches including a monoclonal antibody targeting the cell surface glycosphingolipid disialoganglioside and cytokines successfully eliminate minimal residual disease.

Recent Findings: Since this seminal discovery, clinical trials evaluating immunotherapy in combination with chemotherapy and cellular therapies have begun to demonstrate effectiveness in treatment of bulky disease. Read More

View Article and Full-Text PDF
February 2021

The Inhibitor of Apoptosis Protein Livin Confers Resistance to Fas-Mediated Immune Cytotoxicity in Refractory Lymphoma.

Cancer Res 2020 10 14;80(20):4439-4450. Epub 2020 Sep 14.

Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.

Death receptor Fas-mediated apoptosis not only eliminates nonspecific and autoreactive B cells but also plays a major role in antitumor immunity. However, the possible mechanisms underlying impairment of Fas-mediated induction of apoptosis during lymphomagenesis remain unknown. In this study, we employed our developed syngeneic lymphoma model to demonstrate that downregulation of Fas is required for both lymphoma development and lymphoma cell survival to evade immune cytotoxicity. Read More

View Article and Full-Text PDF
October 2020

Immunotherapy in cervix cancer.

Cancer Treat Rev 2020 Nov 7;90:102088. Epub 2020 Aug 7.

Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy. Electronic address:

The treatment approach to cervix cancer has remained unchanged for several decades and new therapeutic strategies are now required to improve outcomes, as the prognosis is still poor. In the last years, a better understanding of HPV tumor-host immune system interactions and the development of new therapeutics targeting immune checkpoints generated interest in the use of immunotherapy in cervix cancer. Preliminary phase I-II trials demonstrated the efficacy, the duration of responses and the manageable safety of this approach. Read More

View Article and Full-Text PDF
November 2020

GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas.

Am J Cancer Res 2020 1;10(2):674-687. Epub 2020 Feb 1.

Department of Molecular Genetics and Microbiology, University of Florida Gainesville, FL 32610, USA.

Since the prognosis for children with high-risk osteosarcoma (OS) remains suboptimal despite intensive multi-modality therapies, there is a clear and urgent need for the development of targeted therapeutics against these refractory malignancies. Chimeric antigen receptor (CAR) modified T cells can meet this need by utilizing the immune system's potent cytotoxic mechanisms against tumor specific antigen targets with exquisite specificity. Since OS highly expresses the GD2 antigen, a viable immunotherapeutic target, we sought to assess if CAR modified T cells targeting GD2 could induce cytotoxicity against OS tumor cells. Read More

View Article and Full-Text PDF
February 2020

Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization.

J Virol 2020 04 16;94(9). Epub 2020 Apr 16.

Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.

A vaccine to prevent maternal acquisition of human cytomegalovirus (HCMV) during pregnancy is a primary strategy to reduce the incidence of congenital disease. The MF59-adjuvanted glycoprotein B (gB) protein subunit vaccine (gB/MF59) is the most efficacious vaccine tested to date for this indication. We previously identified that gB/MF59 vaccination elicited poor neutralizing antibody responses and an immunodominant response against gB antigenic domain 3 (AD-3). Read More

View Article and Full-Text PDF

TARP is an immunotherapeutic target in acute myeloid leukemia expressed in the leukemic stem cell compartment.

Haematologica 2020 05 1;105(5):1306-1316. Epub 2019 Aug 1.

Cancer Research Institute Ghent, Ghent University, Ghent, Belgium.

Immunotherapeutic strategies targeting the rare leukemic stem cell compartment might provide salvage to the high relapse rates currently observed in acute myeloid leukemia (AML). We applied gene expression profiling for comparison of leukemic blasts and leukemic stem cells with their normal counterparts. Here, we show that the T-cell receptor γ chain alternate reading frame protein (TARP) is over-expressed in pediatric (n=13) and adult (n=17) AML sorted leukemic stem cells and blasts compared to hematopoietic stem cells and normal myeloblasts (15 healthy controls). Read More

View Article and Full-Text PDF

Principles of tumorigenesis and emerging molecular drivers of SHH-activated medulloblastomas.

Ann Clin Transl Neurol 2019 May 19;6(5):990-1005. Epub 2019 Mar 19.

2nd Department of Pediatrics Semmelweis University H-1094 Budapest Hungary.

SHH-activated medulloblastomas (SHH-MB) account for 25-30% of all medulloblastomas (MB) and occur with a bimodal age distribution, encompassing many infant and adult, but fewer childhood cases. Different age groups are characterized by distinct survival outcomes and age-specific alterations of regulatory pathways. Here, we review SHH-specific genetic aberrations and signaling pathways. Read More

View Article and Full-Text PDF

CART Immunotherapy: Development, Success, and Translation to Malignant Gliomas and Other Solid Tumors.

Front Oncol 2018 17;8:453. Epub 2018 Oct 17.

Department of Neurosurgery, IU Simon Cancer Center, IU School of Medicine, Indiana University Purdue University Indianapolis, Indianapolis, IN, United States.

T cell chimeric antigen receptor (CAR) technology has allowed for the introduction of a high degree of tumor selectivity into adoptive cell transfer therapies. Evolution of this technology has produced a robust antitumor immunotherapeutic strategy that has resulted in dramatic outcomes in liquid cancers. CAR-expressing T-cells (CARTs) targeting CD19 and CD20 have been successfully used in the treatment of hematologic malignancies, producing sustained tumor regressions in a majority of treated patients. Read More

View Article and Full-Text PDF
October 2018

A Monoclonal Antibody against 6-Acetylmorphine Protects Female Mice Offspring from Adverse Behavioral Effects Induced by Prenatal Heroin Exposure.

J Pharmacol Exp Ther 2019 01 25;368(1):106-115. Epub 2018 Oct 25.

Section for Drug Abuse Research, Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway (A.M.S.K., J.M.A., E.L.Ø., S.S., I.L.B.); School of Pharmacy, Faculty of Mathematics and Natural Sciences (A.M.S.K., J.M.A., E.L.Ø.), Institute of Basic Medical Sciences (I.L.B.) and Institute of Clinical Medicine (J.M.), Faculty of Medicine, University of Oslo, Oslo, Norway; and Department of Infectious Disease Immunology (A.A.) and Department of Health Data and Digitalization (J.M.), Norwegian Institute of Public Health, Oslo, Norway

Escalating opioid use among fertile women has increased the number of children being exposed to opioids during fetal life. Furthermore, accumulating evidence links prenatal opioid exposure, including opioid maintenance treatment, to long-term negative effects on cognition and behavior, and presses the need to explore novel treatment strategies for pregnant opioid users. The present study examined the potential of a monoclonal antibody (mAb) targeting heroin's first metabolite, 6-acetylmorphine (6-AM), in providing fetal protection against harmful effects of prenatal heroin exposure in mice. Read More

View Article and Full-Text PDF
January 2019

CD8 T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity.

Immunity 2018 10 9;49(4):678-694.e5. Epub 2018 Oct 9.

Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 2M9 Canada; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8 Canada. Electronic address:

CD8 T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8 T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1 cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4 T cell help for its functional generation. Read More

View Article and Full-Text PDF
October 2018