First in-human study of in vivo imaging of ex vivo labeled CAR T cells with dual PET-MR.

Authors

null

Ritu Singla

Cell Therapies, Peter MacCallum Cancer Centre, Melbourne, Australia

Ritu Singla , Dominic M Wall , Samuel Anderson , Nicholas Zia , James C Korte , Lucy Kravets , Gerard McKiernan , Jeanne Butler , Amanda Gammilonghi , Jyoti Arora , Ben J Solomon , Rodney J. Hicks , Timothy Cain , Phillip K. Darcy , Carleen Cullinane , Paul J. Neeson , Rajesh Ramanathan , Ravi Shukla , Vipul Bansal , Simon J. Harrison

Organizations

Cell Therapies, Peter MacCallum Cancer Centre, Melbourne, Australia, Peter MacCallum Cancer Centre, Melbourne, Australia, Sir Ian Potter NanoBioSensing Facility, RMIT University, Melbourne, Australia, Cyclotek (Aust) Pty Ltd, Melbourne, Australia, The University of Melbourne, Melbourne, Australia, Cell Therapies, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, Royal Children Hospital, Melbourne, Australia, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, Australia, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia

Research Funding

Pharmaceutical/Biotech Company
Juno Therapeutics, Australian Global Innovation Linkage Grant

Background: This is a first in human in-vivo biodistribution of ex-vivo labelled CAR T cells assessed in a cohort of patients. Cells were labelled with novel Cu-64 labelled superparamagnetic iron oxide nanoparticles (SPION) and infused IV into patients with solid tumors & tracked using clinical dual PET-MR. The study validates the clinical translation of CAR T cell in-vivo tracking in real time. Methods: Cu-64 radioisotope was bound to silica coated SPION using electrolysis plating with tin & palladium seeding. Cellular uptake of Cu-64 SPION was facilitated with a transfecting agent. Functional assays including 51Chromium release, cytometric bead array demonstrated that labelling process did not affect cytotoxicity & cytokine secretion (TNFα& IFN-g). T cells were transduced with retroviral vector constructs encoding for second-generation chimeric T-cell receptor specific for carbohydrate Lewis Y antigen. Modified T-cells were expanded ex-vivo & were labelled with Cu-64 (~300 MBq) prior to re-infusion (3 x108 labelled cells). Scanning is performed with Siemens 3T dual PET-MR scanner. Results: In this first in human in-vivo study (HREC/16/PMCC/30) a cohort of patients received ex-vivo labelled CAR T cells to determine how many labelled cells distribute to solid tumor sites within 3-5 days. Our results demonstrate that cells can be efficiently labelled (≤60%) with high cell viability (≥85%) at a sensitivity sufficient to detect labelled cells at tumor site for up to 5 days. An observed trend in SUVmean& SUVmax provided insight into efficacy & individual response to therapy. Early time points showed moderate uptake of labelled cells in lungs posterior basal segments without increased activity over next few days, suggesting a transient process. Mild, diffuse bone marrow & relatively intense uptake of labelled cells in liver & spleen suggests margination of cells to reticulo-endothelial system. Distinct PET signal at some of the tumor sites at 24 h suggests antigen specific localization & time taken to reach these sites. Excretion via hepatobiliary indicated reabsorption from GI tract & re-circulation of labelled cells. Minimal uptake in brain & heart supported safety profile of labeling agent. Conclusions: This is first in human in-vivo study to provide highly valuable visual and dynamic data in real time and provides insight into individual responses to therapy. CAR T cell functionality largely remain unchanged due to labeling process. The findings indicate that labelled cells traffic to tumor sites at later time points & remain persistent for extended period of time.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Molecular Diagnostics and Imaging

Clinical Trial Registration Number

HREC/16/PMCC/30

Citation

J Clin Oncol 38: 2020 (suppl; abstr 3557)

DOI

10.1200/JCO.2020.38.15_suppl.3557

Abstract #

3557

Poster Bd #

287

Abstract Disclosures

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