35 results match your criteria Immunotherapeutic Targeting in Children

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

Oncoimmunology 2021 Feb 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

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

Trends Cancer 2020 Dec 16. 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
December 2020

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

Nedd4-Binding Protein 1 and TNFAIP3-Interacting Protein 1 Control MHC-1 Display in Neuroblastoma.

Cancer Res 2018 12 13;78(23):6621-6631. Epub 2018 Sep 13.

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.

: Neuroblastoma is the second most common tumor in children. The cause of neuroblastoma is thought to lie in aberrant development of embryonic neural crest cells and is accompanied by low MHC-1 expression and suppression of the NF-κB transcription factor, thereby gearing cells toward escape from immunosurveillance. Here, we assess regulation of the MHC-1 gene in neuroblastoma to enhance its immunogenic potential for therapeutic T-cell targeting. Read More

View Article and Full-Text PDF
December 2018

The human lymph node microenvironment unilaterally regulates T-cell activation and differentiation.

PLoS Biol 2018 09 4;16(9):e2005046. Epub 2018 Sep 4.

Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Read More

View Article and Full-Text PDF
September 2018

Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies.

Nat Med 2017 Dec 13;23(12):1416-1423. Epub 2017 Nov 13.

Cancer Institute, University College London, London, UK.

Mature T cell cancers are typically aggressive, treatment resistant and associated with poor prognosis. Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy (normal) T cells. Unlike B cell depletion, pan-T cell aplasia is prohibitively toxic. Read More

View Article and Full-Text PDF
December 2017

Programmed cell death ligand 1 (PD-L1) expression is not a predominant feature in Ewing sarcomas.

Pediatr Blood Cancer 2018 Jan 4;65(1). Epub 2017 Sep 4.

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

Background: Programmed cell death 1 (PD-1) receptor engagement on T cells by its ligand programmed cell death ligand 1 (PD-L1) is a key mechanism of immune escape, and antibody blockade of the interaction has emerged as an effective immunotherapeutic strategy in some cancers. The role and relevance of the PD-1 checkpoint in Ewing sarcoma (EwS) is not yet understood.

Procedure: Here, we investigated expression of PD-L1 and PD-1 in EwS by immunohistochemistry analysis of pretherapeutic tumor biopsies and in tumor xenografts following treatment with human T cells engineered to express a chimeric antigen receptor (CAR) against the tumor-associated antigen G . Read More

View Article and Full-Text PDF
January 2018

The neoepitope landscape in pediatric cancers.

Genome Med 2017 08 31;9(1):78. Epub 2017 Aug 31.

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

Background: Neoepitopes derived from tumor-specific somatic mutations are promising targets for immunotherapy in childhood cancers. However, the potential for such therapies in targeting these epitopes remains uncertain due to a lack of knowledge of the neoepitope landscape in childhood cancer. Studies to date have focused primarily on missense mutations without exploring gene fusions, which are a major class of oncogenic drivers in pediatric cancer. Read More

View Article and Full-Text PDF

New targeted therapies for relapsed pediatric acute lymphoblastic leukemia.

Expert Rev Anticancer Ther 2017 08 5;17(8):725-736. Epub 2017 Jul 5.

a Division of Pediatric Hematology Oncology, Department of Pediatrics , Perlmutter Cancer Center, NYU Langone Medical Center , New York , NY , USA.

Introduction: The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Read More

View Article and Full-Text PDF

Roles of cancer/testis antigens (CTAs) in breast cancer.

Cancer Lett 2017 07 6;399:64-73. Epub 2017 Mar 6.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University. Nanjing 210004, China. Electronic address:

Breast cancer is the most common cancer diagnosed and is the second leading cause of cancer death among women in the US. For breast cancer, early diagnosis and efficient therapy remains a significant clinical challenge. Therefore, it is necessary to identify novel tumor associated molecules to target for biomarker development and immunotherapy. Read More

View Article and Full-Text PDF

The Safety of available immunotherapy for the treatment of glioblastoma.

Expert Opin Drug Saf 2017 Mar 3;16(3):277-287. Epub 2017 Jan 3.

a Duke Brain Tumor Immunotherapy Program, Department of Neurosurgery , Duke University Medical Center , Durham , NC , USA.

Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Read More

View Article and Full-Text PDF

Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.

Immunotherapy 2016 09;8(9):1097-117

Department of Human Oncology, University of Wisconsin, Madison, WI, USA.

Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Read More

View Article and Full-Text PDF
September 2016

Immunotherapeutic approaches for the treatment of childhood, adolescent and young adult non-Hodgkin lymphoma.

Br J Haematol 2016 05 7;173(4):597-616. Epub 2016 Apr 7.

Department of Pediatrics, New York Medical College, Valhalla, NY, USA.

With the introduction of the anti-CD20 monoclonal antibody rituximab, B-cell non-Hodgkin lymphoma was the first malignancy successfully treated with an immunotherapeutic agent. Since then, numerous advances have expanded the repertoire of immunotherapeutic agents available for the treatment of a variety of malignancies, including many lymphoma subtypes. These include the introduction of monoclonal antibodies targeting a variety of cell surface proteins, including the successful targeting of immunoregulatory checkpoint receptors present on T-cells or tumour cells. Read More

View Article and Full-Text PDF

Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein.

Blood 2015 Jul 3;126(5):629-39. Epub 2015 Jun 3.

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;

Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting the CD19 B cell-associated protein have demonstrated potent activity against relapsed/refractory B-lineage acute lymphoblastic leukemia (B-ALL). Not all patients respond, and CD19-negative relapses have been observed. Overexpression of the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2) occurs in a subset of adults and children with B-ALL and confers a high risk of relapse. Read More

View Article and Full-Text PDF

Immunobiology and immunotherapeutic targeting of glioma stem cells.

Adv Exp Med Biol 2015 ;853:139-66

Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Los Angeles, CA, 90048, USA.

For decades human brain tumors have confounded our efforts to effectively manage and treat patients. In adults, glioblastoma multiforme is the most common malignant brain tumor with a patient survival of just over 14 months. In children, brain tumors are the leading cause of solid tumor cancer death and gliomas account for one-fifth of all childhood cancers. Read More

View Article and Full-Text PDF

Programmed cell death ligand 1 expression in osteosarcoma.

Cancer Immunol Res 2014 Jul 21;2(7):690-698. Epub 2014 Apr 21.

Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, United States.

Programmed cell death ligand 1 (PDL1, also known as B7H1) is a cell-surface protein that suppresses the cytotoxic CD8(+) T-cell-mediated immune response. PDL1 expression and its clinical relevance in sarcomas are not well understood. Therefore, we sought to measure RNA expression levels for PDL1 in 38 clinically annotated osteosarcoma tumor samples and aimed to determine if PDL1 expression correlates with clinical features and tumor-infiltrating lymphocytes (TIL). Read More

View Article and Full-Text PDF

B7-H3-mediated tumor immunology: Friend or foe?

Int J Cancer 2014 Jun 30;134(12):2764-71. Epub 2013 Sep 30.

Cancer Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

B7-H3 (CD276), a newly identified member of the B7 family of molecules, is often induced in human tumors and its overexpression is closely correlated with survival, prognosis or tumor grade. Although cancer immunotherapy has not been completely translated into clinical successes, interest has been further enhanced by the realization of these costimulatory molecules' potential as targets to modulate clinical immune responses. Despite ample evidence implicating B7-H3 in tumor immune escape, a steady flow of reports have suggested that it may also have antitumor effects under certain circumstances. Read More

View Article and Full-Text PDF

Highlights of the third International Conference on Immunotherapy in Pediatric Oncology.

Pediatr Hematol Oncol 2013 Aug 12;30(5):349-66. Epub 2013 Jun 12.

Department for Stem Cell Transplantation and Immunology, J.W. Goethe-University Hospital, University Hospital for Children and Adolescents, Frankfurt/Main, Germany.

The third International Conference on Immunotherapy in Pediatric Oncology was held in Frankfurt/Main, Germany, October 1-2, 2012. Major topics of the conference included (i) cellular therapies using antigen-specific and gene-modified T cells for targeting leukemia and pediatric solid tumors; (ii) overcoming hurdles and barriers with regard to immunogenicity, immune escape, and the role of tumor microenvironment; (iii) vaccine strategies and antigen presentation; (iv) haploidentical transplantation and innate immunity; (v) the role of immune cells in allogeneic transplantation; and (vi) current antibody/immunoconjugate approaches for the treatment of pediatric malignancies. During the past decade, major advances have been made in improving the efficacy of these modalities and regulatory hurdles have been taken. Read More

View Article and Full-Text PDF

Targeting EpCAM (CD326) for immunotherapy in hepatoblastoma.

Oncoimmunology 2013 Jan;2(1):e22620

Department of Paediatric Surgery and Urology; University Children's Hospital; Tuebingen, Germany.

Hepatoblastoma (HB) is the most common liver cancer in children. Recurrence of HB after chemotherapy and surgery is frequent among high-risk patients and is associated with chemoresistance. Immunotherapy may improve poor treatment outcomes in HB patients. Read More

View Article and Full-Text PDF
January 2013

The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.

Br J Cancer 2012 Mar 28;106(6):1123-33. Epub 2012 Feb 28.

Department of Pediatric Haematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer-Campus 1, Muenster, 48149, Germany.

Background: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer.

Methods: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. Read More

View Article and Full-Text PDF

A current viewpoint of lymphangioleiomyomatosis supporting immunotherapeutic treatment options.

Am J Respir Cell Mol Biol 2012 Jan;46(1):1-5

Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University, Chicago, Illinois, USA.

Lymphangioleiomyomatosis (LAM) leads to hyperproliferation of abnormal smooth muscle cells in the lungs, associated with diffuse pulmonary parenchymal cyst formation and progressive dyspnea on exertion. The disease targets women of child-bearing age. Complications include pneumothoraces and chylous pleural effusions. Read More

View Article and Full-Text PDF
January 2012

Highlights of the second international conference on "Immunotherapy in Pediatric Oncology".

Pediatr Hematol Oncol 2011 Sep;28(6):459-60

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

The Second International Conference on Immunotherapy in Pediatric Oncology was held in Houston, Texas, USA, October 11-12, 2010, to discuss the progress and challenges that have occurred in cutting edge immunotherapeutic strategies currently being developed for pediatric oncology. Major topics included immune targeting of acute lymphoblastic leukemia and pediatric solid tumors, chimeric antigen receptors (CARs) for hematologic malignancies and solid tumors, enhancing graft-versus-leukemia for pediatric cancers, overcoming hurdles of immunotherapy, strategies to active the innate immune system, and moving immunotherapy beyond phase I studies. Significant progress has been made in the last 2 years both in the development of novel immunobiologics such as CARs, and in establishing survival benefits of an anti-GD2 monoclonal antibody in randomized studies. Read More

View Article and Full-Text PDF
September 2011