Targeted immunotherapies for anaplastic lymphoma kinase-positive pediatric tumors - current advances and future perspectives

Sep 22, 2026

Targeted immunotherapies for anaplastic lymphoma kinase (ALK)-positive pediatric tumors are reviewed with emphasis on current advances and future perspectives. Pediatric cancer remains a leading cause of childhood and adolescent mortality, while standard modalities often cause severe long-term toxicities and many patients face relapse or refractory disease. ALK acts as a key oncogenic driver in multiple pediatric malignancies, and although ALK tyrosine kinase inhibitors can benefit patients, resistance motivates alternative strategies. The review highlights ALK-directed immunotherapies including vaccines, ALK CAR-T and other cellular approaches, and ALK-targeting antibodies, focusing on rationale and preclinical efficacy with implications for safer, more durable disease control.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Editorial on the research topic: Next-Generation Treatment for Pediatric Cancer

Rationale for ALK as a molecular target

Scope of the review and key immunotherapy modalities

Keywords

TYPE Review PUBLISHED 14 August 2026 DOI 10.3389/fimmu.2026.1912199 OPEN ACCESS EDITED BY Federica Riccardo, University of Turin, Italy REVIEWED BY Amitabh Singh, Vardhman Mahavir Medical College & Safdarjung Hospital, India Lianna Jean Marks, Stanford University, United States Mahdi Mehmandoost, Shahid Beheshti University of Medical Sciences, Iran *CORRESPONDENCE Claudia Voena claudia.voena@unito. it Roberto Chiarle roberto. chiarle@unito. it †These authors have contributed equally to this work RECEIVED 17 June 2026 REVISED 21 July 2026 ACCEPTED 24 July 2026 PUBLISHED 14 August 2026 CITATION Maccagno M, Tagliero R, Chiarle R and Voena C (2026) Targeted immunotherapies for anaplastic lymphoma kinase-positive pediatric tumors: current advancesand future perspectives. Front. Immunol. 17:1912199 . doi: 10.3389/fimmu.2026.1912199 COPYRIGHT © 2026 Maccagno, Tagliero, Chiarle and Voena. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Targeted immunotherapies for anaplastic lymphoma kinasepositive pediatric tumors: current advances and future perspectives Monica Maccagno 1†, Roberta Tagliero 1†, Roberto Chiarle 1,2,3* and Claudia Voena 1* 1 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy, 2 Department of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy, 3 Department of Pathology, Children’s Hospital and Harvard Medical School, Boston, MA, United States Editorial on the research topic: Next-Generation Treatment for Pediatric Cancer: Advancing Immunotherapy through Combinations. Cancer remains one of the leading causes of disease-related mortality among children and adolescents. Despite advances in treatments, outcomes for many pediatric tumors remain limited, particularly in patients with high-risk, relapsed, or refractory disease. Standard therapies, including surgery, chemotherapy, radiotherapy, and stem cell transplantation, are frequently associated with severe long-term toxicities and secondary malignancies. Resistance and relapse remain major clinical challenges. Recent progress in cancer immunotherapy has revolutionized adult oncology, and remarkable clinical advances have been observed in several pediatric cancers. However, comparable beneﬁts in most solid tumors remain limited. Among molecular targets, anaplastic lymphoma kinase (ALK) has emerged as a critical driver of tumorigenesis in several pediatric malignancies, including anaplastic large cell lymphoma (ALCL), neuroblastoma and inﬂammatory myoﬁbroblastic tumor. While ALK tyrosine kinase inhibitors have demonstrated clinical beneﬁt, the emergence of resistance highlights the need for alternative or complementary strategies. ALK can act as an oncoantigen, as shown by spontaneous ALK-speciﬁc humoral and T-cell responses in patients with ALKpositive ALCL, and ALK-directed immunotherapies have been developed and have shown efﬁcacy in preclinical models of ALK-positive tumors, including ALCLand neuroblastoma. Therefore, ALK-directed immunotherapies represent biologically rational and promising approaches that may, if proven safe and effective in clinical trials, address resistance and improve long-term disease control. In this review, we will discuss ALK-speciﬁc immunotherapies, including ALK vaccines, ALK CAR-T and other cellular therapies, as well as ALK-targeting antibodies with a particular focus on pediatric ALK-positive tumors. KEYWORDS ALK-positive tumors, anaplastic lymphoma kinase (ALK), antibody-drug co

FAQs

Why are targeted immunotherapies needed for ALK-positive pediatric tumors?

Standard pediatric therapies can lead to severe long-term toxicities, and many patients still experience resistance, relapse, or refractory disease. ALK-directed immunotherapies are presented as biologically rational options that may help address these challenges, including resistance to ALK tyrosine kinase inhibitors.

What role does ALK play in pediatric malignancies?

ALK is described as a critical driver of tumorigenesis in several pediatric cancers, including ALCL, neuroblastoma, and inflammatory myofibroblastic tumor. ALK is also characterized as an oncoantigen supported by ALK-specific humoral and T-cell responses in ALK-positive ALCL patients.

Which ALK-directed immunotherapy approaches are discussed in the review?

The review covers ALK-specific immunotherapies including ALK vaccines, ALK CAR-T and other cellular therapies, and ALK-targeting antibodies. It focuses particularly on pediatric ALK-positive tumors.

Sep 22, 2026

Upload by CatatanPagi