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. 2019 Jul 23;9:10634. doi: 10.1038/s41598-019-46938-7

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Assessment of in vivo activity of AIC100 by tumor elimination, T cell imaging, and survival. (A) A weekly measurement of whole body luminescence to detect tumor growth or killing by AIC100. Luminescence intensity is pseudocolored in the range of 10³–10⁵ photons/sec/mm². Time elapsed after tumor xenograft is shown in weeks. (B) PET/CT imaging by ¹⁸F-NOTAOCT to image CAR T cell distribution. Images are maximum intensity projections of the entire mouse body (~20-mm-thick plane). PET intensity is pseudocolored in the range of 1–10% injection dose/cm³. (C) Longitudinal imaging of tumor and AIC100 distribution dynamics, illustrating the occurrence of T cell peak (week 3) post tumor peak (week 2), followed by contraction of T cells. (D) Tumor burden in lungs was estimated by the level of luminescence. Mice were treated with AIC100 (P1 to P5 batches used at 1X or MTD), no T cells (No T), non-transduced T cells at MTD (NT), or F292A CAR 2^nd generation (41BB-CD3ζ) at MTD. (E) Survival curves of 8505C xenografted mice comparing no treatment (n = 19), treatment with NT T cells (n = 11), and treatment with 1X (n = 19) and MTD (n = 27) CAR T cells until 100 days post xenograft.