Promise and challenges of clinical non-invasive T-cell tracking in the era of cancer immunotherapy

Abstract

In the last decades, our understanding of the role of the immune system in cancer has significantly improved and led to the discovery of new immunotherapeutic targets and tools, which boosted the advances in cancer immunotherapy to fight a growing number of malignancies. Approved immunotherapeutic approaches are currently mainly based on immune checkpoint inhibitors, antibody-derived targeted therapies, or cell-based immunotherapies. In essence, these therapies induce or enhance the infiltration and function of tumor-reactive T cells within the tumors, ideally resulting in complete tumor eradication. While the clinical application of immunotherapies has shown great promise, these therapies are often accompanied either by a variety of side effects as well as partial or complete unresponsiveness of a number of patients. Since different stages of disease progression elicit different local and systemic immune responses, the ability to longitudinally interrogate the migration and expansion of immune cells, especially T cells, throughout the whole body might greatly facilitate disease characterization and understanding. Furthermore, it can serve as a tool to guide development as well as selection of appropriate treatment regiments. This review provides an overview about a variety of immune-imaging tools available to characterize and study T-cell responses induced by anti-cancer immunotherapy. Moreover, challenges are discussed that must be taken into account and overcome to use immune-imaging tools as predictive and surrogate markers to enhance assessment and successful application of immunotherapies.

Current state and upcoming opportunities for immunoPET biomarkers in lung cancer

“…Features of monoclonal antibodies (mAbs) and related molecules are shown. Abbreviations: Fab: fragment antigen-binding, F(ab)2: bivalent fragment antigen-binding, mAb: monoclonal antibody, ScFv: single chain variable fragment [10,13].…”

“…Commonly used radionuclides for PET imaging [10,13]. response to treatment, where the patient group with enhanced tumor tracer uptake showed a better response and higher progression free survival (PFS) and OS.…”

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

“…Tc. Их физические свойства (период полураспада, энергия излучения) и особенности хелатирования определяет тип используемой молекулы-носителя [35,51]. В иммуноонкологии используются в основном 18 F, 68 Ga, 89 Zr, 99m Tc.…”

“…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).…”

Recent Advances in Exosomal miRNA Biosensing for Liquid Biopsy

“…Therefore, it is of great significance to explore noninvasive strategies for accurate early tumor diagnosis and monitor. Unlike noninvasive imaging for cancer monitoring [ 5 , 6 ], liquid biopsy is a technique that detects, analyzes, and monitors tumors by analyzing various body fluid samples such as blood or urine [ 7 ]. Compared with traditional tissue biopsy techniques that are limited to tumor progression at a single timepoint and suffer from bias due to tumor heterogeneity, liquid biopsy is one of the frontier hotspots in tumor diagnosis because it is less invasive, is convenient for multiple sampling, and can monitor tumor progression in real time.…”