ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1546441

This article is part of the Research TopicNovel Clinical and Translational Insights in Cell Therapies for CancerView all 7 articles

Trained autologous PBMCs for immunotherapy of neuroblastoma

Provisionally accepted
  • 1Children’s National Hospital, Washington D.C., United States
  • 2George Washington University, Washington, D.C., District of Columbia, United States
  • 3New York University, New York City, New York, United States

The final, formatted version of the article will be published soon.

Background: Pediatric solid tumors, particularly neuroblastoma, present significant treatment challenges due to the limited efficacy of existing therapies. Adoptive immunotherapy, which involves transferring immune cells has shown clinical promise. Optimizing the preparation of immune cells ex vivo is critical to enhancing tumor immunity. This study introduces a novel method for improving the efficacy of autologous peripheral blood mononuclear cells (PBMCs) for neuroblastoma treatment.Methods: An IRB-approved protocol was used to collect tumor samples and PBMCs from eight patients undergoing neuroblastoma biopsy or resection. Primary tumor cells were isolated, cultured, and characterized using Phox2b and synaptophysin staining. Autologous PBMCs were co-cultured with irradiated tumor cells pre-treated with MYC inhibitors (I-BET726, JQ1) and a STING antagonist (C170) to enhance immunogenicity and train tumor-specific PBMCs. The immunogenicity and gene expression changes in treated tumor cells were assessed through multiplex ELISA and NanoString Tumor Signaling profiling. The phenotype and cytotoxicity of the trained PBMCs were evaluated by flow cytometry, IFN-γ ELISA, and IncuCyte assays.Results: Trained PBMCs primarily induced potent tumor cell cytotoxicity in patient-derived cellular products. In a preclinical neuroblastoma mouse model, similarly trained splenocytes demonstrated powerful efficacy, mirroring the findings in patient-derived PBMCs. This approach generates immunogenic tumor cells through modulation with small molecule inhibitors and radiation, enabling PBMCs or splenocytes to induce cytotoxic trained autologous tumor-specific T cells under controlled in vitro conditions. These trained PBMCs and splenocytes exhibit potent cytotoxicity against neuroblastoma, with significant therapeutic effects as an adoptive cellular immunotherapy in vivo.Conclusions: This study provides preliminary evidence supporting the efficacy of a personalized, PBMC-based immunotherapy for neuroblastoma. These findings highlight the potential for further development of this approach as a novel treatment strategy, paving the way for improved clinical outcomes in pediatric oncology.

Keywords: Neuroblastoma, training, autologous PBMCs, T cells, Immunotherapy

Received: 16 Dec 2024; Accepted: 19 May 2025.

Copyright: © 2025 Wu, Basu, Wright, Li, Petrosyan, Nelson, Shea, Yarmarkovich and Sandler. 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) or licensor 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.

* Correspondence: Anthony Sandler, Children’s National Hospital, Washington D.C., United States

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