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CAR T-cell therapy: a potential treatment strategy for pediatric midline gliomas

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Abstract

Pediatric brain tumors are the primary cause of death in children with cancer. Diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG) are frequently unresectable due to their difficult access location, and 5-year survival remains less than 20%. Despite significant advances in tumor biology and genetics, treatment options remain limited and ineffective. Immunotherapy using T cells with a chimeric antigen receptor (CAR) that has been genetically engineered is quickly emerging as a new treatment option for these patients. High levels of expression were detected for both disialoganglioside (GD2) and B7-H3 in pediatric DMG/DIPG. Numerous studies have been conducted in recent years employing various generations of GD2-CAR T cells. The two most prevalent adverse effects found with this therapy are cytokine release syndrome, which varies in severity from mild constitutional symptoms to a high-grade disease associated with potentially fatal multi-organ failure, and neurotoxicity, known as CAR T-cell-related encephalopathy syndrome. During the acute phase of anticancer action, peri-tumoral neuro-inflammation might cause deadly hydrocephalus. The initial results of clinical trials show that the outcomes are not highly encouraging as B cell malignancies and myelomas. In vivo research on CAR T-cell therapy for DIPG has yielded encouraging results, but in human trials, the early results have shown potentially fatal side effects and very modest, but fleeting improvements. Solid tumors present a hindrance to CAR T-cell therapy because of the antigenic dilemma and the strong immune-suppressing tumor microenvironment.

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Acknowledgements

The authors acknowledge all professors and consultants in the Department of Neurosurgery for their guidance and assistance.

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  1. Anand Kumar Das and Mainak Sinha contributed equally to the work.

Authors and Affiliations

  1. All India Institute of Medical Sciences, Phulwari Sharif, Patna, Bihar, 801507, India

    Anand Kumar Das, Mainak Sinha & Saraj Kumar Singh

  2. SMS Medical College and Hospital, Jaipur, Rajasthan, India

    Anurag Chaudhary & Manish Agrawal

  3. Gauhati Medical College, Guwahati, Assam, India

    Ashim Kumar Boro

  4. ESIC Medical College and Hospital, Patna, Bihar, India

    Sona Bhardwaj

  5. Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

    Simmi Kishore

  6. Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India

    Katyayani Kumari

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Anand Kumar Das and Saraj Kumar Singh contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Anand Kumar Das, Mainak Sinha, Saraj Kumar Singh, Anurag Chaudhary, Ashim Kumar Boro, Manish Agrawal, Sona Bhardwaj, Simmi Kishore, and Katyayani Kumari. The first draft of the manuscript was written by Anand Kumar Das and Mainak Sinha. Both contributed equally to the work*. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Das, A.K., Sinha, M., Singh, S.K. et al. CAR T-cell therapy: a potential treatment strategy for pediatric midline gliomas. Acta Neurol Belg (2024). https://doi.org/10.1007/s13760-024-02519-8

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