Smart probes for optical imaging of T cells and screening of anti-cancer immunotherapies

Bertolini, Marco; Wong, Man Sing; Mendive‐Tapia, Lorena; Vendrell, Marc

doi:10.1039/d2cs00928e

Cited by 17 publications

(7 citation statements)

References 147 publications

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“…These probes, therefore, can be used as realtime in vivo imaging agents. [82] Targeting metabolism-associated enzymes found in the tumor immune landscape such as those involved in nucleoside salvage pathway [83] and kynurenine pathway [84] has shown encouraging results for predicting immunotherapy response. Examples of small molecule metabolism-targeting probes include 18 F-FAC [85][86] and 18 F-CFA [87] (Figure 5A), radiolabeled substrates of deoxycytidine kinase (dCK) which is the rate-limiting enzyme in the nucleoside salvage pathway proliferating CD8 + T cells utilize for DNA synthesis [88] and 1-L-[ 18 F]-FETrp [89] (Figure 5B), a PET tracer developed to monitor indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan metabolism that contributes to the immunosuppressive TME associated with poor clinical outcomes.…”

Section: Substrate and Activity-based Imaging Probesmentioning

confidence: 99%

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

Kazim,

Yoo

2023

Angew Chem Int Ed

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The last two decades have witnessed a major revolution in the field of tumor immunology including clinical progress using various immunotherapy strategies. These advances have highlighted the potential for approaches that harness the power of the immune system to fight against cancer. While cancer immunotherapies have shown significant clinical successes, patient responses vary widely due to the complex and heterogeneous nature of tumors and immune responses, calling for reliable biomarkers and therapeutic strategies to maximize the benefits of immunotherapy. Especially, stratifying responding individuals from non‐responders during early stages of treatment could help avoid long‐term damages and tailor personalized treatments. In efforts to develop non‐invasive means for accurately evaluating and predicting tumor response to immunotherapy, multiple affinity‐based agents targeting immune cell markers and checkpoint molecules have been developed and advanced to clinical trials. In addition, researchers have recently turned their attention to substrate and activity‐based imaging probes that can provide real‐time, functional assessment of immune response to treatment. Here, we highlight some of those recently designed probes that image functional proteases as biomarkers of cancer immunotherapy with a focus on their chemical design and detection modalities and discuss challenges and opportunities for the development of imaging tools utilized in cancer immunotherapy.

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Section: Substrate and Activity-based Imaging Probesmentioning

confidence: 99%

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

Kazim,

Yoo

2023

Angew Chem Int Ed

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“…9 Among various emerging strategies, fluorescence imaging has revolutionized the analysis of biological systems due to its advantages in temporal and spatial sampling, response rate, and high sensitivity, as well as non-radioactive characteristics. 10–13 Fluorescence imaging can be categorized into non-targeted and targeted fluorescence imaging to visualize and study different molecules or structures in biological samples. 14 Non-targeted fluorescent probes typically do not possess high specificity for a particular target biological molecule, and they may interact with multiple molecules.…”

Section: Introductionmentioning

confidence: 99%

A FAPI-conjugated FITC fluorescence probe for targeted cancer imaging

Wu,

Zhou,

Zhang

et al. 2024

New J. Chem.

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“…The tandem-locked optical probes have been developed for real-time tracking and noninvasive interpretation of the profiles, distribution, and functions of immune cells in tumors during cancer immunotherapy. − It has been revealed that the immunotherapy efficacy varies with the infiltration of different immune cells, and detection of tumor-infiltrated immune cells could be applied for prognostic stratification and targeted therapy. , Mast cells, a prominent subset of tissue-resident immune cells, play a crucial role in allergic and other inflammatory diseases . However, their functions in modulation of the tumor immune microenvironment have been less understood.…”

Section: Introductionmentioning

confidence: 99%

Bienzyme-Locked Activatable Fluorescent Probes for Specific Imaging of Tumor-Associated Mast Cells

Hu,

Yu,

et al. 2024

J. Am. Chem. Soc.

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Tumor-associated mast cells (TAMCs) have been recently revealed to play a multifaceted role in the tumor microenvironment. Noninvasive optical imaging of TAMCs is thus highly desired to gain insights into their functions in cancer immunotherapy. However, due to the lack of a single enzyme that is specific to mast cells, a common probe design approach based on single-enzyme activation is not applicable. Herein, we reported a bienzyme-locked molecular probe (THC MC ) based on a photoinduced electron transfer-intramolecular charge-transfer hybrid strategy for in vivo imaging of TAMCs. The bienzyme-locked activation mechanism ensures that THC MC exclusively turns on near-infrared (NIR) fluorescence only in the presence of both tryptase and chymase specifically coexpressed by mast cells. Thus, THC MC effectively distinguishes mast cells from other leukocytes, including T cells, neutrophils, and macrophages, a capability lacking in single-locked probes. Such a high specificity of THC MC allows noninvasive tracking of the fluctuation of TAMCs in the tumor of living mice during cancer immunotherapy. The results reveal that the decreased intratumoral signal of THC MC after combination immunotherapy correlates well with the reduced population of TAMCs, accurately predicting the inhibition of tumor growth. Thus, this study not only presents the first NIR fluorescent probe specific for TAMCs but also proposes a generic bienzymelocked probe design approach for in vivo cell imaging.

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Smart probes for optical imaging of T cells and screening of anti-cancer immunotherapies

Abstract: T cells are an essential component of the immune system and display multiple biological functions. Smart probes range from small fluorophores to nanoconstructs, and can target metabolic and enzymatic biomarkers as well as cell-surface receptors.

Cited by 17 publications

References 147 publications

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

A FAPI-conjugated FITC fluorescence probe for targeted cancer imaging

Bienzyme-Locked Activatable Fluorescent Probes for Specific Imaging of Tumor-Associated Mast Cells

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