Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI

Kennis, Bridget; Michel, Keith A.; Brugmann, William; Laureano, Álvaro Macedo; Tao, Rong; Somanchi, Srinivas S.; Einstein, Samuel A.; Bravo-Alegría, Javiera; Maegawa, Satoru; Wahba, Andrew; Kiany, Simin; Gordon, Nancy; Silla, Lúcia Mariano da Rocha; Schellingerhout, Dawid; Khatua, Soumen; Zaky, Wafik; Sandberg, David I.; Cooper, Laurence J.N.; Lee, Dean A.; Bankson, James A.; Gopalakrishnan, Vidya

doi:10.1007/s11060-019-03091-5

Cited by 29 publications

(35 citation statements)

References 50 publications

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“…19F MRI is another direct method which involves direct spin detection of the biologically safe isotope fluorine-19, enabling highly sensitive and quantitative "hot-spot" imaging as seen with PET/SPECT studies. One study demonstrated labeling of intracerebrally administered natural killer cells with fluorine-19, which importantly showed no cytotoxicity and change in NK cell therapeutic efficacy (109). In another study, 19F labeling of glial-progenitor cells transplanted into an ALS animal model was not found alter capacity for astrocyte differentiation (Figure 5B) (106).…”

Section: Mri-based Techniquesmentioning

confidence: 98%

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

et al. 2021

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Stem cell and immune cell therapies are being investigated as a potential therapeutic modality for CNS disorders, performing functions such as targeted drug or growth factor delivery, tumor cell destruction, or inflammatory regulation. Despite promising preclinical studies, delivery routes for maximizing cell engraftment, such as stereotactic or intrathecal injection, are invasive and carry risks of hemorrhage and infection. Recent developments in MRI-guided focused ultrasound (MRgFUS) technology have significant implications for treating focal CNS pathologies including neurodegenerative, vascular and malignant processes. MRgFUS is currently employed in the clinic for treating essential tremor and Parkinson's Disease by producing precise, incisionless, transcranial lesions. This non-invasive technology can also be modified for non-destructive applications to safely and transiently open the blood-brain barrier (BBB) to deliver a range of therapeutics, including cells. This review is meant to familiarize the neuro-interventionalist with this topic and discusses the use of MRgFUS for facilitating cellular delivery to the brain. A detailed and comprehensive description is provided on routes of cell administration, imaging strategies for targeting and tracking cellular delivery and engraftment, biophysical mechanisms of BBB enhanced permeability, supportive proof-of-concept studies, and potential for clinical translation.

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Section: Mri-based Techniquesmentioning

confidence: 98%

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

et al. 2021

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“…Novel cell labeling agents have been developed and tested in rodent and nonhuman primate models and could be useful for evaluating NK cell kinetics and trafficking in the canine osteosarcoma model. Ex vivo-expanded human NK cells labeled with the non-radioactive isotope fluorine 19 ( 19 F) can be detected in rodent tissues by NMR and imaged with 19 F-MRI (65,66). Similarly, expanded NK cells from rhesus macques were labeled with 89 zirconium-oxine ( 89 Zr-oxine) cell labeling and quantitated and imaged with positron emission tomography (PET)/CT (67).…”

Section: Clinical Application Of Adoptive Nk Cell Immunotherapy In Canine Osteosarcomamentioning

confidence: 99%

“…As the use of genetically modified cells in humans has even more significant regulatory hurdles to overcome compared to similar trials in dogs, clinical trials in dogs can speed the evaluation of novel approaches, identify those that are more promising, and provide additional useful safety data to inform subsequent human trials. As noted above, because of the ability to easily acquire patient biospecimens, including tumor biopsies, and the relatively comparable size to humans, the model is ideal for investigating effects on tumor targeting achieved with different CAR-NK constructs and for studying novel NK cell labeling and imaging techniques (65)(66)(67).…”

Section: Future Applicationsmentioning

confidence: 99%

Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma

Kisseberth

Lee

2021

Front. Vet. Sci.

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Osteosarcoma is the most common primary bone tumor in both humans and dogs. It is a highly metastatic cancer and therapy has not improved significantly since the inclusion of adjuvant chemotherapy into disease treatment strategies. Osteosarcoma is an immunogenic tumor, and thus development of immunotherapies for its treatment, especially treatment of microscopic pulmonary metastases might improve outcomes. NK cells are lymphocytes of the innate immune system and can recognize a variety of stressed cells, including cancer cells, in the absence of major histocompatibility complex (MHC)-restricted receptor ligand interactions. NK cells have a role in controlling tumor progression and metastasis and are important mediators of different therapeutic interventions. The core hypothesis of adoptive natural killer (NK) cell therapy is there exists a natural defect in innate immunity (a combination of cancer-induced reduction in NK cell numbers and immunosuppressive mechanisms resulting in suppressed function) that can be restored by adoptive transfer of NK cells. Here, we review the rationale for adoptive NK cell immunotherapy, NK cell biology, TGFβ and the immunosuppressive microenvironment in osteosarcoma, manufacturing of ex vivo expanded NK cells for the dog and provide perspective on the present and future clinical applications of adoptive NK cell immunotherapy in spontaneous osteosarcoma and other cancers in the dog.

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“…While significant research is underway in adult glioblastoma multiforme, there has been limited progress in the use of NK cells as a platform for immunotherapy in childhood brain tumors even though studies of the tumor microenvironment in children suggest that they may be more amenable to NK cell cytotoxicity [51]. There are emerging studies of 19 F-labeled NK cells in the treatment and localization of NK cell activity for medulloblastoma, the commonest childhood brain tumor, which can potentially lead to further progress in this field [52]. There are also other ongoing studies involving local injection of ex vivo expanded autologous NK cells via an ommaya reservoir for children with posterior fossa brain tumors (ClinicalTrials.gov Identifier: NCT02271711), as well as non-myeloablative haploidentical stem cell transplantation in phase II trials (ClinicalTrials.gov Identifier: NCT02100891); however, preliminary results are still unavailable.…”

Section: Natural Killer Cells In Solid Tumorsmentioning

confidence: 99%

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers

Kimpo

Lee

2019

Curr Oncol Rep

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Purpose of Review We aim to review the most recent findings in the use of NK cells in childhood cancers. Recent Findings Natural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less likelihood of cytokine storm. Cytotoxicity to solid tumors (rhabdomyosarcoma, Ewing’s sarcoma, neuroblastoma) is seen with graft versus tumor effect in transplant and in combination with antibodies. Challenges lie in the microenvironment which is suppressive for NK cells. Summary NK cell immunotherapy in childhood cancers is promising and recent works aim to overcome challenges.

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Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI

Cited by 29 publications

References 50 publications

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications

Adoptive Natural Killer Cell Immunotherapy for Canine Osteosarcoma

The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers

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