Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy

Abstract

Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy. As we improve our understanding of the orchestrated cellular and molecular mechanisms involved in ACT, this will provide biologic insight and improved ACT strategies for pediatric malignancies. This review focuses on ACT strategies outside of chimeric antigen receptor T-cell therapy, including completed and ongoing clinical trials, and highlights promising preclinical data in tumor-infiltrating lymphocytes that enhance the clinical efficacy of ACT for high-risk pediatric solid tumors.

Trial registration: ClinicalTrials.gov NCT03645928.

Conflict of interest statement

Conflicts of Interest and Source of Funding: J. Mullinax: Moffitt Cancer Center has licensed intellectual property (IP) related to the proliferation and expansion of tumor-infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. He is an inventor on such IP. He participates in sponsored research agreements with Iovance Biotherapeutics, Intellia Therapeutics, and SQZ Biotech, which are not related to this research. He has received research support that is not related to this research from the following entities: NIH-NCI (K08CA252642), Ocala Royal Dames, and V Foundation. He has received ad hoc consulting fees from Merit Medical. S.P.-T.: Moffitt Cancer Center has licensed IP related to the proliferation and expansion of TILs to Iovance Biotherapeutics. Moffitt has also licensed IP to Tuhura Biopharma. She is an inventor on such IP. She is listed as a coinventor on a patent application with Provectus Biopharmaceuticals. She participates in sponsored research agreements with Provectus Biopharmaceuticals, Iovance Biotherapeutics, Intellia Therapeutics, Dyve Biosciences, and Turnstone Biologics, which are not related to this research. She has received research support that is not related to this research from the following entities: NIH-NCI (U01 CA244100-01, R01 CA259387, R43 CA257552-01A1, and R01 CA239219-01A1), Swim Across America, and V Foundation. She has received ad hoc consulting fees from Seagen Inc. and serves as an advisor for KSQ Therapeutics. For the remaining authors, none were declared.

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