Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents

Parijat Bhatnagar; Mian Alauddin; James A. Bankson; Dickson Kirui; Payam Seifi; Helen Huls; Dean A. Lee; Aydin Babakhani; Mauro Ferrari; King C. Li; Laurence J.N. Cooper

doi:10.1038/srep04502

Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents

Parijat Bhatnagar, Mian Alauddin, James A. Bankson, Dickson Kirui, Payam Seifi, Helen Huls, Dean A. Lee, Aydin Babakhani, Mauro Ferrari, King C. Li, Laurence J.N. Cooper

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

28 Scopus citations

Abstract

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION- 64 Cu). This can now be potentially used for 64 Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR + SPION pos T cells effectively target in vitro CD19 + lymphoma.

Original language	English (US)
Article number	4502
Journal	Scientific reports
Volume	4
DOIs	https://doi.org/10.1038/srep04502
State	Published - Mar 28 2014

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Monoclonal Antibody Facility
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10.1038/srep04502

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@article{d640bd78a38340b49d46fdfdf4534d00,

title = "Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents",

abstract = "Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION- 64 Cu). This can now be potentially used for 64 Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR + SPION pos T cells effectively target in vitro CD19 + lymphoma.",

author = "Parijat Bhatnagar and Mian Alauddin and Bankson, {James A.} and Dickson Kirui and Payam Seifi and Helen Huls and Lee, {Dean A.} and Aydin Babakhani and Mauro Ferrari and Li, {King C.} and Cooper, {Laurence J.N.}",

note = "Funding Information: We thank Dr. Carl June at the University of Pennsylvania for help generating and providing the aAPC (clone 4), Dr. Perry Hackett at the University of Minnesota for help with the SB system. We acknowledge the support of Immunology Imaging Core (HEI 1S10RR029552-01), NCI Cancer Center (P30 CA016672) and the flow cytometry core at MD Anderson Cancer Center. P.B. thanks Prof. Mehmet Toner, Massachusetts General Hospital; Dr. Harjeet Singh, Hillary G. Caruso, MDACC. This work was supported by funding from: Alliance for NanoHealth Department of Defense Telemedicine & Advanced Technology Research Center (W81XWH-09-02-0139, W81XWH-10-02-0125); Center for Transport Oncophysics – Physical Science Oncology Center at The Methodist Hospital Research Institute (U54 CA143837); ARCO Foundation Young Teacher-Investigator Award and the Naman Family Fund for Basic Research.",

year = "2014",

month = mar,

day = "28",

doi = "10.1038/srep04502",

language = "English (US)",

volume = "4",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents

AU - Bhatnagar, Parijat

AU - Alauddin, Mian

AU - Bankson, James A.

AU - Kirui, Dickson

AU - Seifi, Payam

AU - Huls, Helen

AU - Lee, Dean A.

AU - Babakhani, Aydin

AU - Ferrari, Mauro

AU - Li, King C.

AU - Cooper, Laurence J.N.

N1 - Funding Information: We thank Dr. Carl June at the University of Pennsylvania for help generating and providing the aAPC (clone 4), Dr. Perry Hackett at the University of Minnesota for help with the SB system. We acknowledge the support of Immunology Imaging Core (HEI 1S10RR029552-01), NCI Cancer Center (P30 CA016672) and the flow cytometry core at MD Anderson Cancer Center. P.B. thanks Prof. Mehmet Toner, Massachusetts General Hospital; Dr. Harjeet Singh, Hillary G. Caruso, MDACC. This work was supported by funding from: Alliance for NanoHealth Department of Defense Telemedicine & Advanced Technology Research Center (W81XWH-09-02-0139, W81XWH-10-02-0125); Center for Transport Oncophysics – Physical Science Oncology Center at The Methodist Hospital Research Institute (U54 CA143837); ARCO Foundation Young Teacher-Investigator Award and the Naman Family Fund for Basic Research.

PY - 2014/3/28

Y1 - 2014/3/28

N2 - Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION- 64 Cu). This can now be potentially used for 64 Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR + SPION pos T cells effectively target in vitro CD19 + lymphoma.

AB - Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION- 64 Cu). This can now be potentially used for 64 Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR + SPION pos T cells effectively target in vitro CD19 + lymphoma.

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Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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Monoclonal Antibody Facility (MAF)

Cite this

Tumor lysing genetically engineered t cells loaded with multi-modal imaging agents

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

Other files and links

Fingerprint

Equipment

Monoclonal Antibody Facility (MAF)

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