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In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.


ABSTRACT: Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies.

SUBMITTER: Pittet MJ 

PROVIDER: S-EPMC1941490 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

Pittet Mikael J MJ   Grimm Jan J   Berger Cedric R CR   Tamura Takahiko T   Wojtkiewicz Gregory G   Nahrendorf Matthias M   Romero Pedro P   Swirski Filip K FK   Weissleder Ralph R  

Proceedings of the National Academy of Sciences of the United States of America 20070718 30


Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimension  ...[more]

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