Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice

Ana Caterina Parente-Pereira; Jerome Burnet; David Ellison; Julie Foster; David Marc Davies; Sjoukje van der Stegen; Sophie Burbridge; Laura Chiapero-Stanke; Scott Wilkie; Stephen Mather; John Maher

doi:10.1007/s10875-011-9532-8

Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice

Ana Caterina Parente-Pereira, Jerome Burnet, David Ellison, Julie Foster, David Marc Davies, Sjoukje van der Stegen, Sophie Burbridge, Laura Chiapero-Stanke, Scott Wilkie, Stephen Mather, John Maher

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

93 Citations (Scopus)

Abstract

Adoptive immunotherapy using chimeric antigen receptor-engrafted T cells is a promising emerging therapy for cancer. Prior to clinical testing, it is mandatory to evaluate human therapeutic cell products in meaningful in vivo pre-clinical models. Here, we describe the use of fused single-photon emission CT-CT imaging to monitor real-time migration of chimeric antigen receptor-engineered T cells in immune compromised (SCID Beige) mice. Following intravenous administration, human T cells migrate in a highly similar manner to that reported in man, but penetrate poorly into established tumors. By contrast, when delivered via intraperitoneal or subcutaneous routes, T cells remain at the site of inoculation with minimal systemic absorption-irrespective of the presence or absence of tumor. Together, these data support the validity of pre-clinical testing of human T-cell immunotherapy in SCID Beige mice. In light of their established efficacy, regional administration of engineered human T cells represents an attractive therapeutic option to minimize toxicity in the treatment of selected malignancies.

Original language	English
Pages (from-to)	710 - 718
Number of pages	9
Journal	Journal of Clinical Immunology
Volume	31
Issue number	4
DOIs	https://doi.org/10.1007/s10875-011-9532-8
Publication status	Published - 2011

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Parente-Pereira, A. C., Burnet, J., Ellison, D., Foster, J., Davies, D. M., van der Stegen, S., Burbridge, S., Chiapero-Stanke, L., Wilkie, S., Mather, S., & Maher, J. (2011). Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice. Journal of Clinical Immunology, 31(4), 710 - 718. https://doi.org/10.1007/s10875-011-9532-8

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title = "Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice",

abstract = "Adoptive immunotherapy using chimeric antigen receptor-engrafted T cells is a promising emerging therapy for cancer. Prior to clinical testing, it is mandatory to evaluate human therapeutic cell products in meaningful in vivo pre-clinical models. Here, we describe the use of fused single-photon emission CT-CT imaging to monitor real-time migration of chimeric antigen receptor-engineered T cells in immune compromised (SCID Beige) mice. Following intravenous administration, human T cells migrate in a highly similar manner to that reported in man, but penetrate poorly into established tumors. By contrast, when delivered via intraperitoneal or subcutaneous routes, T cells remain at the site of inoculation with minimal systemic absorption-irrespective of the presence or absence of tumor. Together, these data support the validity of pre-clinical testing of human T-cell immunotherapy in SCID Beige mice. In light of their established efficacy, regional administration of engineered human T cells represents an attractive therapeutic option to minimize toxicity in the treatment of selected malignancies.",

author = "Parente-Pereira, {Ana Caterina} and Jerome Burnet and David Ellison and Julie Foster and Davies, {David Marc} and {van der Stegen}, Sjoukje and Sophie Burbridge and Laura Chiapero-Stanke and Scott Wilkie and Stephen Mather and John Maher",

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doi = "10.1007/s10875-011-9532-8",

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Parente-Pereira, AC, Burnet, J, Ellison, D, Foster, J, Davies, DM, van der Stegen, S, Burbridge, S, Chiapero-Stanke, L, Wilkie, S, Mather, S & Maher, J 2011, 'Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice', Journal of Clinical Immunology, vol. 31, no. 4, pp. 710 - 718. https://doi.org/10.1007/s10875-011-9532-8

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T1 - Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice

AU - Parente-Pereira, Ana Caterina

AU - Burnet, Jerome

AU - Ellison, David

AU - Foster, Julie

AU - Davies, David Marc

AU - van der Stegen, Sjoukje

AU - Burbridge, Sophie

AU - Chiapero-Stanke, Laura

AU - Wilkie, Scott

AU - Mather, Stephen

AU - Maher, John

PY - 2011

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N2 - Adoptive immunotherapy using chimeric antigen receptor-engrafted T cells is a promising emerging therapy for cancer. Prior to clinical testing, it is mandatory to evaluate human therapeutic cell products in meaningful in vivo pre-clinical models. Here, we describe the use of fused single-photon emission CT-CT imaging to monitor real-time migration of chimeric antigen receptor-engineered T cells in immune compromised (SCID Beige) mice. Following intravenous administration, human T cells migrate in a highly similar manner to that reported in man, but penetrate poorly into established tumors. By contrast, when delivered via intraperitoneal or subcutaneous routes, T cells remain at the site of inoculation with minimal systemic absorption-irrespective of the presence or absence of tumor. Together, these data support the validity of pre-clinical testing of human T-cell immunotherapy in SCID Beige mice. In light of their established efficacy, regional administration of engineered human T cells represents an attractive therapeutic option to minimize toxicity in the treatment of selected malignancies.

AB - Adoptive immunotherapy using chimeric antigen receptor-engrafted T cells is a promising emerging therapy for cancer. Prior to clinical testing, it is mandatory to evaluate human therapeutic cell products in meaningful in vivo pre-clinical models. Here, we describe the use of fused single-photon emission CT-CT imaging to monitor real-time migration of chimeric antigen receptor-engineered T cells in immune compromised (SCID Beige) mice. Following intravenous administration, human T cells migrate in a highly similar manner to that reported in man, but penetrate poorly into established tumors. By contrast, when delivered via intraperitoneal or subcutaneous routes, T cells remain at the site of inoculation with minimal systemic absorption-irrespective of the presence or absence of tumor. Together, these data support the validity of pre-clinical testing of human T-cell immunotherapy in SCID Beige mice. In light of their established efficacy, regional administration of engineered human T cells represents an attractive therapeutic option to minimize toxicity in the treatment of selected malignancies.

U2 - 10.1007/s10875-011-9532-8

DO - 10.1007/s10875-011-9532-8

M3 - Article

VL - 31

SP - 710

EP - 718

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

IS - 4

ER -

Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice

Abstract

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