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Opportunities and challenges in the immunological therapy of pediatric malignancy: a concise snapshot

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Abstract

Over the last 50 years, collaborative clinical trials have reduced the number of children dying from pediatric cancer significantly. Unfortunately, certain tumor types have remained resistant to conventional surgical, radiotherapy and chemotherapy combinations, and relapsing and/or refractory disease remains associated with dismal outcomes. Recently, renewed attention has been given to the role for immunotherapies in pediatric oncology. In fact, these combine several attractive features, including (but possibly not limited to) the specificity for cancer cells, potentially in vivo persistence and longevity, and potency against refractory disease. In this narrative review designed for the academic pediatrician, we will concisely review the biological underpinnings behind the immunological therapy of pediatric neoplasms and illustrate the current humoral, cellular approaches, and novel drugs targeting the immune checkpoint, oncolytic viruses, and tumor vaccines. We will also comment on the future directions, challenges, and open questions faced by the field.

What is Known:

• Cancer immunotherapy drives immune cells and its humoral weaponry to eliminate tumor cells.

• This occurs by recognizing antigens ideally expressed only on tumoral, but not normal/healthy, cells.

What is New:

• Clinical immunotherapy trials have shown responses in children with relapsing/refractory neoplasms.

• Novel humoral/cellular immunotherapies, immune checkpoint inhibitors, oncolytic viruses, and tumor vaccines are currently being investigated in pediatric oncology.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

BV:

Brentuximab vedotin

CAR:

Chimeric antigen receptor

CNS:

Central nervous system

COG:

Children’s Oncology Group (USA)

CRS:

Cytokine release syndrome

CT:

Computed tomography

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

DC:

Dendritic cell

DNA:

Deoxyribonucleic acid

FDA:

Food and Drug Administration (USA)

FDG-PET:

Fluorodeoxyglucose positron emission tomography

GD-2:

Disialoganglioside 2

GM-CSF:

Granulocyte/macrophage-colony stimulating factor

HLA:

Human leukocyte antigen

mAb:

Monoclonal antibody

MHC:

Major histocompatibility complex

MRD:

Minimal residual disease

NBL:

Neuroblastoma

NCI:

National Cancer Institute (USA)

NCT:

National Clinical Trial (USA)

OV:

Oncolytic virus

PD-1:

Programmed death receptor 1

PTLD:

Post-transplantation lymphoproliferative disorder

RNA:

Ribonucleic acid

TAA:

Tumor associated antigen

TCR:

T cell receptor

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Authors and Affiliations

  1. Pediatric Hematology-Oncology Research Laboratory & Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-Child, University Hospital of Lausanne, Lausanne, Switzerland

    Francesco Ceppi, Maja Beck-Popovic & Raffaele Renella

  2. Leukemia Research Program and Division of Pediatric Oncology, University Children’s Hospital Zurich, Zurich, Switzerland

    Jean-Pierre Bourquin

Authors
  1. Francesco Ceppi
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  2. Maja Beck-Popovic
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  3. Jean-Pierre Bourquin
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  4. Raffaele Renella
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Contributions

FC reviewed the literature and co-wrote the manuscript. MBP reviewed the literature and co-wrote the manuscript. JPB reviewed the literature and co-wrote the manuscript. RR reviewed the literature and co-wrote the manuscript.

Corresponding author

Correspondence to Raffaele Renella.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

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Communicated by Mario Bianchetti

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Ceppi, F., Beck-Popovic, M., Bourquin, JP. et al. Opportunities and challenges in the immunological therapy of pediatric malignancy: a concise snapshot. Eur J Pediatr 176, 1163–1172 (2017). https://doi.org/10.1007/s00431-017-2982-0

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  • DOI: https://doi.org/10.1007/s00431-017-2982-0

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