Radionuclide-based molecular imaging allows CAR-T cellular visualization and therapeutic monitoring

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is a new and effective form of adoptive cell therapy that is rapidly entering the mainstream for the treatment of CD19-positive hematological cancers because of its impressive effect and durable responses. Huge challenges remain in achieving similar success in patients with solid tumors. The current methods of monitoring CAR-T, including morphological imaging (CT and MRI), blood tests, and biopsy, have limitations to assess whether CAR-T cells are homing to tumor sites and infiltrating into tumor bed, or to assess the survival, proliferation, and persistence of CAR-T cells in solid tumors associated with an immunosuppressive microenvironment. Radionuclide-based molecular imaging affords improved CAR-T cellular visualization and therapeutic monitoring through either a direct cellular radiolabeling approach or a reporter gene imaging strategy, and endogenous cell imaging is beneficial to reflect functional information and immune status of T cells. Focusing on the dynamic monitoring and precise assessment of CAR-T therapy, this review summarizes the current applications of radionuclide-based noninvasive imaging in CAR-T cells visualization and monitoring and presents current challenges and strategic choices.

Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response

“…Molecular imaging is an interdisciplinary field which fuses molecular biology with medical imaging [ 37 , 71 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. When exploited for immunotherapy, it holds dual promise: Providing new insights into the mechanisms underlying the interactions between the host tissue, the tumor, and the immunotherapeutic agent.…”

Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

“…In addition to boosting local expression of multiple cytokines and promoting vascular normalization, radiotherapy could activate endogenous target antigen-specific immunity to yield complementary benefits, thereby maximizing the effect of CAR-T cells 183 - 185 . Radionuclide-based molecular imaging afforded the visualization and therapeutic monitoring of CAR-T cells through cellular radiolabeling approach or gene imaging strategies in determining whether CAR-T cells homed and infiltrated into the tumor bed, as well as their survival and persistence in TIME 186 . The endogenous cell imaging could reflect the immune status and functional information of T cells and even delineate the developmental trajectory of immune cells.…”

Potential of Theranostics in Visualisation of the Tumour Microenvironment and Elimination of Its Immunosuppressive Components

“…Область их применения -визуализация мишеней в микроокружении и мониторинг CAR-Tтерапии (табл. 4) [52].…”

“…Клинические исследования ряда диагностических радиофармпрепаратов были прерваны вследствие радиотоксических эффектов в отношении цитототоксических лимфоцитов и Т-хелперов 1-го типа. В исследовании по мониторингу клеточной терапии с использованием химерных Т-клеточных рецепторов продемонстрировано, что изотопы вызывают апоптоз части клеток, хотя эффект этот выражен слабо и клинически был не значим [51,52]. Во-вторых, хелатирование может изменять третичную структуру молекул адресной доставки, что особенно выражено при использовании низкомолекулярных компонентов (нанободи, аффибоди, пептиды).…”