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European Journal of Pediatrics

, Volume 176, Issue 9, pp 1163–1172 | Cite as

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

  • Francesco Ceppi
  • Maja Beck-Popovic
  • Jean-Pierre Bourquin
  • Raffaele Renella
Review

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.

Keywords

Immunotherapy Pediatric hematology-oncology Childhood Cancer 

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

Notes

Authors’ 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.

Compliance with ethical standards

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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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Pediatric Hematology-Oncology Research Laboratory & Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department Woman-Mother-ChildUniversity Hospital of LausanneLausanneSwitzerland
  2. 2.Leukemia Research Program and Division of Pediatric OncologyUniversity Children’s Hospital ZurichZurichSwitzerland

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