CAR-T and CAR-NK therapies in pediatric oncology: opportunities and challenges

Malignant diseases in children remain one of the most difficult areas of modern oncology, where even significant progress in diagnosis and standard treatment methods does not always allow for stable disease control. Over the past decade, cellular immune technologies have attracted special attention, primarily CAR-T and CAR-NK therapies, which have opened up the possibilities of targeted effects on tumors and demonstrated unprecedented effectiveness in recurrent B-cell leukemias. CAR-T cells made it possible to change the prognosis for patients who have lost sensitivity to traditional therapy regimens, and CAR-NK presented the prospect of a safer, potentially universal platform. However, the successful results in hematological diseases contrast sharply with the difficulties of using these technologies in solid tumors and rare childhood oncopathologies. Heterogeneity of antigens, features of the tumor microenvironment, low infiltration and insufficient cell persistence remain the main barriers limiting the expansion of indications. Additional challenges include immunotoxicity, variability in clinical outcomes, and complexity in the production of cellular products, especially in pediatrics. The review examines the key mechanisms of action of CAR-therapies, the specifics of their effectiveness and safety in children, as well as modern strategies for improving effectiveness, from multiantigenic and tandem designs to combined approaches and methods of personalized monitoring. Particular attention is being paid to areas of future research, including response biomarkers, monitoring of minimal residual disease, and integration of cellular technologies with other therapies.

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