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PET imaging of T cells derived from umbilical cord blood

Leukemia volume 23, pages 620–622 (2009)Cite this article

Progress in understanding tumor-specific immune responses, genetic engineering and ex vivo manufacturing, have led to improvements in the safety and feasibility of adoptive transfer of genetically modified T cells. However, rational design, application and evaluation of T-cell therapy requires monitoring methods that can detect, locate and serially quantify these cell-mediated immune responses. Currently, such monitoring methods are chiefly limited to invasive techniques to investigate recovered cell populations for in vitro measurements including histology, flow cytometry, Q-PCR or the detection of cytokines. These assays provide episodic glimpses of the bio distribution of T cells and are limited by the number and sites of sampling. In contrast, imaging provides a methodology for quantitative, non-invasive, longitudinal and spatial in vivo information about the dynamic processes of infused T cells.

In earlier studies, in vivo imaging of lymphocyte migration used cells passively labeled with radiotracers ex vivo. An alternative imaging approach involves stable transduction/transfection of cells with a reporter gene (such as herpes simplex virus-1 thymidine kinase; HSV-TK) that can be visualized by active accumulation of a radiolabeled reporter probe. It has been demonstrated that cells genetically modified to express HSV-TK could be imaged by scintigraphy or positron emission tomography (PET) in rodents after infusions of I-labeled 2′-fluoro-2′-deoxy-1-β-D-arabinofuranosyl-5-iodouracil.1 Bioluminescence imaging (BLI) of luciferase reporter gene expression has also been used to monitor lymphocyte trafficking in a mouse model.2, 3 Recently Dobrenkov et al.4 have shown the feasibility of PET and BLI in a prostate cancer model using peripheral blood chimeric antigen receptor (CAR)+ cells and Jensen and co-workers have evaluated the biodistribution of CAR+ T cells by magnetic resonance imaging.5

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References

  1. Tjuvajev JG, Avril N, Oku T, Sasajima T, Miyagawa T, Joshi R et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 1998; 58: 4333–4341.

    CAS  PubMed  Google Scholar 

  2. Singh H, Serrano LM, Pfeiffer T, Olivares S, McNamara G, Smith DD et al. Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. Cancer Res 2007; 67: 2872–2880.

    Article  CAS  Google Scholar 

  3. Serrano LM, Pfeiffer T, Olivares S, Numbenjapon T, Bennitt J, Kim D et al. Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy. Blood 2006; 107: 2643–2652.

    Article  CAS  Google Scholar 

  4. Dobrenkov K, Olszewska M, Likar Y, Shenker L, Gunset G, Cai S et al. Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging. J Nucl Med 2008; 49: 1162–1170.

    Article  Google Scholar 

  5. Lazovic J, Jensen MC, Ferkassian E, Aguilar B, Raubitschek A, Jacobs RE . Imaging immune response in vivo: cytolytic action of genetically altered T cells directed to glioblastoma multiforme. Clin Cancer Res 2008; 14: 3832–3839.

    Article  CAS  Google Scholar 

  6. Cooper LJ, Topp MS, Serrano LM, Gonzalez S, Chang WC, Naranjo A et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect. Blood 2003; 101: 1637–1644.

    Article  CAS  Google Scholar 

  7. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719–1724.

    Article  CAS  Google Scholar 

  8. Soghomonyan S, Hajitou A, Rangel R, Trepel M, Pasqualini R, Arap W et al. Molecular PET imaging of HSV1-tk reporter gene expression using [18F]FEAU. Nat Protoc 2007; 2: 416–423.

    Article  CAS  Google Scholar 

  9. Jensen MC, Popplewell L, DiGiusto DL, Kalos M, Cooper LJN, Raubitschek A et al. A first-in-human clinical trial of adoptive therapy using CD19-specific chimeric antigen receptor re-directed T cells for recurrent/refractory follicular lymphoma. Mol Ther 2007; 15: S142.

    Google Scholar 

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Acknowledgements

Support from Cancer Center Core Grant (CA16672); RO1 (CA124782, CA120956); R21 (CA129390, CA116127); DOD (PR064229); The Alliance for Cancer Gene Therapy; The Alex Lemonade Stand Foundation; The Carl C Anderson, Sr and Marie Jo Anderson Charitable Foundation; The Gillson Longenbaugh Foundation; The JP McCarthy Fund Developmental Grant Program The Leukemia and Lymphoma Society; The Lymphoma Research Foundation; The Miller Foundation, The National Foundation for Cancer Research; The National Marrow Donor Program; The Pediatric Cancer Research Foundation.

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Authors and Affiliations

  1. Division of Pediatrics, U.T. M. D. Anderson Cancer Center, Houston, TX, USA

    H Singh, S Olivares, P R Manuri, H Huls, D A Lee & L J N Cooper

  2. Division of Experimental Diagnostic Imaging, U.T. M. D. Anderson Cancer Center, Houston, TX, USA

    A M Najjar, R Nishii, U Mukhopadhyay & M Alauddin

  3. Department of Medicine, Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX, USA

    G Dotti & C Bollard

  4. Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    P J Simmons

  5. Division of Stem Cell Transplantation, U.T. M. D. Anderson Cancer Center, Houston, TX, USA

    E J Shpall, R E Champlin & J G Gelovani

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  1. H Singh
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  15. J G Gelovani
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  16. L J N Cooper
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Correspondence to L J N Cooper.

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Singh, H., Najjar, A., Olivares, S. et al. PET imaging of T cells derived from umbilical cord blood. Leukemia 23, 620–622 (2009). https://doi.org/10.1038/leu.2008.256

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