In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.
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.
Pittet
Mikael J
MJ
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA. mpittet@mgh.harvard.edu
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
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement; D016219:Immunotherapy, Adoptive; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015898:Tomography Scanners, X-Ray Computed
D000941:Antigens