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