Advancing Immune and Cell-Based Therapies Through Imaging

Ponomarev, Vladimir

doi:10.1007/s11307-017-1069-7

Cited by 17 publications

(10 citation statements)

References 95 publications

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“…In terms of multiplexing breadth at single-cell levels, scRNAseq is unmatched in the information provided: gene expression profiles can be used to subset cells, identify unique surface markers, and trace lineages. This information complements molecular imaging, as the unique cellular markers can be used to map cell subsets across time and space in a minimally-invasive manner, including across other types of immune cells such as T-cells [177][178][179][180][181]. When used in this way a single gene, a signature, or even a cell type can become a biomarker to guide drug discovery efforts.…”

Section: Discussionmentioning

confidence: 97%

Macrophage imaging and subset analysis using single-cell RNA sequencing

Arlauckas

Weissleder

et al. 2021

Nanotheranostics

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Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies. Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging the intrinsic capacity of macrophages to accumulate nanomaterials in their role as professional phagocytes. Unfortunately, current clinical imaging modalities are limited in their ability to quantify broad molecular programs that may explain (a) which particular cell subsets a given imaging agent is actually labeling, and (b) what mechanistic role those cells play in promoting drug response or resistance. Highly multiplexed single-cell approaches including single-cell RNA sequencing (scRNAseq) have emerged as resources to help answer these questions. In this review, we query recently published scRNAseq datasets to support companion macrophage imaging, with particular focus on using dextran-based nanoparticles to predict the action of anti-cancer nanotherapies and monoclonal antibodies.

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Section: Discussionmentioning

confidence: 97%

Macrophage imaging and subset analysis using single-cell RNA sequencing

Arlauckas

Weissleder

et al. 2021

Nanotheranostics

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“…The utility of these methods for CAR T-cell tracking has yet to be evaluated. Finally, serial imaging studies with probes binding to T-cell-inhibiting and -activating molecules, such as CTLA-4, PD-1/PD-L1, LAG-3, IL-2R, and OX40 (26)(27)(28), may enable understanding of interactions between CAR T-cells and the tumor microenvironment and, potentially, provide real-time response assessment.…”

Section: Real-time Applicationmentioning

confidence: 99%

Imaging of CAR T-Cells in Cancer Patients: Paving the Way to Treatment Monitoring and Outcome Prediction

et al. 2019

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In 2013, the journal Science named cancer immunotherapy as the ''breakthrough of the year'' based on targeted approaches using chimeric antigen receptor (CAR) T-cells. CD19-specific CAR T-cell therapy has revolutionized the treatment landscape for patients with relapsed B-cell acute lymphocytic leukemia (1,2). Similar successes have not been seen in patients with solid tumors, in part because of inconsistent expression of specific tumor antigens and physical impediments to T-cell trafficking, for example, for passing the blood-brain barrier or reaching metastatic disease in bone marrow. Other factors interfering with prolonged response to CAR T-cell therapy include loss of target antigen and T-cell exhaustion. These resistance mechanisms may be alleviated by CARs targeting 2 or more tumor antigens (NCT03019055), more sophisticated T-cell engineering techniques, or combination therapies of CARs with various immune checkpoint inhibitors. So far, it has remained unclear why certain cell therapies succeed and even provide durable clinical responses (1,2) whereas others fail (3). Ideal monitoring of CAR T-cell therapies should include the ability to track T-cell migration, engagement with the antigenbearing tumor cells, as well as T-cell expansion and persistence at the tumor site-all essential steps for therapeutic efficacy. Imaging studies might perhaps also enable timely intervention to avoid potentially lethal systemic toxicity. Current clinical methods to monitor the infused cells include serum profiling of cytokines associated with T-cell activation, direct enumeration of tumorspecific T-cells in peripheral blood, and (repeated) tumor biopsies. Overall, the in vivo activation dynamics of engineered immune cells remain incompletely understood, as no means of real-time monitoring of the intratumoral milieu currently exists. PRINCIPLES OF CELL TRACKING Cell tracking by imaging requires the direct or indirect labeling of cells. Direct labeling is relatively simple and has been used clinically for several decades, for instance, with 99m Tc or 111 Inlabeled leukocytes. More recently, 89 Zr-oxine has been used for cell labeling and PET imaging (4). As a major disadvantage, the

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“…In addition, other key mediators in immune cell activation/inactivation and various types of cells involved in immune regulation offer additional potential targets for imaging response to immunotherapy [97]. Novel, potential targets and targeting agents are currently under investigation [98]. A list of immunotargets and targeting concepts is shown in Table 4.…”

Section: Tracers To Target the Immune Systemmentioning

confidence: 99%

Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development, Molecular Imaging and Applied Diagnostics; March 14–16, 2018; Vienna, Austria

Lim

Beyer²,

Babayan

et al. 2019

Mol Imaging Biol

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Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to largescale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting Blumpologyf or a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking BWhat can we do with our expertise to help patients?K

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Advancing Immune and Cell-Based Therapies Through Imaging

Cited by 17 publications

References 95 publications

Macrophage imaging and subset analysis using single-cell RNA sequencing

Macrophage imaging and subset analysis using single-cell RNA sequencing

Imaging of CAR T-Cells in Cancer Patients: Paving the Way to Treatment Monitoring and Outcome Prediction

Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development, Molecular Imaging and Applied Diagnostics; March 14–16, 2018; Vienna, Austria

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