Multiparameter Longitudinal Imaging of Immune Cell Activity in Chimeric Antigen Receptor T Cell and Checkpoint Blockade Therapies.

Abstract

Longitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for the assessment of cytotoxic T lymphocyte mediated cancer cell killing. G-SNAT was found to specifically detect the activity of granzyme B within the cytotoxic granules of activated T cells and engaged cancer cells in vitro. In lymphoma tumor-bearing mice, the retention of cyanine 5 labeled G-SNAT-Cy5 correlated to CAR T cell mediated granzyme B exocytosis and tumor eradication. In colorectal tumor-bearing transgenic mice with hematopoietic cells expressing firefly luciferase, longitudinal bioluminescence and fluorescence imaging revealed that after combination treatment of anti-PD-1 and anti-CTLA-4, the dynamics of immune cell trafficking, tumor infiltration, and cytotoxic activity predicted the therapeutic outcome before tumor shrinkage was evident. These results support further development of G-SNAT for imaging early immune response to checkpoint blockade and CAR T-cell therapy in patients and highlight the utility of multimodality imaging for improved mechanistic insights into cancer immunotherapy.

• Authors: Jinghang Xie, Fadi El Rami, Kaixiang Zhou, Federico Simonetta, Zixin Chen, Xianchuang Zheng, Min Chen, Preethi B Balakrishnan, Sheng-Yao Dai, Surya Murty, Israt S Alam, Jeanette Baker, Robert S Negrin, Sanjiv S Gambhir, Jianghong Rao
• Journal: ACS central science (ACS Cent Sci) Vol. 8 Issue 5 Pg. 590-602 (May 25 2022) ISSN: 2374-7943 [Print] United States
• PMID: 35647285 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Published by American Chemical Society.