Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Simonetta, Federico; Alam, Israt S.; Lohmeyer, Juliane K.; Sahaf, Bita; Good, Zinaida; Chen, Wei-Yu; Xiao, Zunyu; Hirai, Toshihito; Scheller, Lukas; Engels, Pujan; Vermesh, Ophir; Robinson, Elise; Haywood, Tom; Sathirachinda, Ataya; Baker, Jeanette; Malipatlolla, Meena; Schultz, Liora; Spiegel, Jay Y.; Miklos, David B.; Mackall, Crystal L.; Negrin, Robert S.

doi:10.1158/1078-0432.ccr-20-2770

Cited by 52 publications

(29 citation statements)

References 44 publications

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“…Based on this work, 89 Zr-DFO-ICOS mAb PET/CT has recently been used to visualize CAR-T cell activation. Significantly higher PET signal was detected in the bone marrow of mice with systemic B-cell lymphoma mice treated with CD19 CAR-T cells, which reflected their distribution and activation 139 .…”

Section: Endogenous Cell Imaging Methodsmentioning

confidence: 94%

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

Shao¹,

Long²,

Ji³

et al. 2021

Theranostics

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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.

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Section: Endogenous Cell Imaging Methodsmentioning

confidence: 94%

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

Shao¹,

Long²,

Ji³

et al. 2021

Theranostics

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“…Due to high sensitivity of PET and SPECT, higher than that of MRI techniques, much lower concentrations of radiolabeled compounds can be used, making possible to avoid interference with cell function and viability (168,171). Using a 89 Zr-labeled anti-ICOS antibody, it was shown that PET can be a useful tool for in vivo tracking of CAR T cells in an orthotopic murine tumor model of lymphoma (172). One disadvantage of PET and SPECT being that they have a limited spatial resolution, combination with CT provides a first approach to surpass this limitation (173).…”

Section: In Vivo Monitoring Of Cellular Products and Treatment Efficacymentioning

confidence: 99%

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma

2021

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Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the major breakthroughs in cancer immunotherapy in the last decade. Outstanding results in hematological malignancies and encouraging pre-clinical anti-tumor activity against a wide range of solid tumors have made CAR T cells one of the most promising fields for cancer therapies. CAR T cell therapy is currently being investigated in solid tumors including glioblastoma (GBM), a tumor for which survival has only modestly improved over the past decades. CAR T cells targeting EGFRvIII, Her2, or IL-13Rα2 have been tested in GBM, but the first clinical trials have shown modest results, potentially due to GBM heterogeneity and to the presence of an immunosuppressive microenvironment. Until now, the use of autologous T cells to manufacture CAR products has been the norm, but this approach has several disadvantages regarding production time, cost, manufacturing delay and dependence on functional fitness of patient T cells, often reduced by the disease or previous therapies. Universal “off-the-shelf,” or allogeneic, CAR T cells is an alternative that can potentially overcome these issues, and allow for multiple modifications and CAR combinations to target multiple tumor antigens and avoid tumor escape. Advances in genome editing tools, especially via CRISPR/Cas9, might allow overcoming the two main limitations of allogeneic CAR T cells product, i.e., graft-vs.-host disease and host allorejection. Here, we will discuss how allogeneic CAR T cells could allow for multivalent approaches and alteration of the tumor microenvironment, potentially allowing the development of next generation therapies for the treatment of patients with GBM.

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“…HSV1-TK transduced lymphocytes and CD19 CAR T cells with truncated epithelial growth factor receptors have been used to provide a platform for both the imaging and tracking of cellular response, as well as the incorporation of suicide genes for safety in the setting of severe T cell immunologic response or graft vs. host disease [168,169]. Recently, a rodent model has adopted the use of 89 ZrDFO-Inducible T-Cell COStimulator (ICOS)-monoclonal antibody (ICOS-ImmunoPET), taking advantage of elevated ICOS in activated CAR-T cells and thereby tracking response and localization [170]. Multiple studies using novel PET isotopes incorporated with either MRI or CT are under study to improve diagnostic accuracy in GVHD, cellular therapy, and immune-based therapeutics.…”

Section: Imaging Of Immunotherapy and Cellular Therapymentioning

confidence: 99%

Molecular Imaging of Inflammatory Disease

et al. 2021

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Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.

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Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Cited by 52 publications

References 44 publications

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

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

Allogeneic CAR T Cells: An Alternative to Overcome Challenges of CAR T Cell Therapy in Glioblastoma

Molecular Imaging of Inflammatory Disease

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