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


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.


Immunotherapy Pediatric hematology-oncology Childhood Cancer 



Acute lymphoblastic leukemia


Brentuximab vedotin


Chimeric antigen receptor


Central nervous system


Children’s Oncology Group (USA)


Cytokine release syndrome


Computed tomography


Cytotoxic T lymphocyte-associated protein 4


Dendritic cell


Deoxyribonucleic acid


Food and Drug Administration (USA)


Fluorodeoxyglucose positron emission tomography


Disialoganglioside 2


Granulocyte/macrophage-colony stimulating factor


Human leukocyte antigen


Monoclonal antibody


Major histocompatibility complex


Minimal residual disease




National Cancer Institute (USA)


National Clinical Trial (USA)


Oncolytic virus


Programmed death receptor 1


Post-transplantation lymphoproliferative disorder


Ribonucleic acid


Tumor associated antigen


T cell receptor


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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