The therapeutic landscape for cells engineered with chimeric antigen receptors

Matthew MacKay^{1

2

3

4}, Ebrahim Afshinnekoo^{1

2

3}, Jonathan Rub^{1

3}, Ciaran Hassan⁵, Mihir Khunte⁵, Nithyashri Baskaran⁵, Bryan Owens⁵, Lauren Liu⁵, Gail J Roboz⁶, Monica L Guzman⁶, Ari M Melnick⁶, Shixiu Wu^{7

8}, Christopher E Mason^{9

10

11

12}

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
² The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.
³ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
⁴ Tri-Institutional Computational Biology and Medicine Program, Weill Cornell Medicine of Cornell University, New York, NY, USA.
⁵ Yale University, New Haven, CT, USA.
⁶ Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
⁷ National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Shenzhen, China. wushixiu@zju.edu.cn.
⁸ Chinese Academy of Medical Science, Peking Union Medical College, Shenzhen, China. wushixiu@zju.edu.cn.
⁹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹⁰ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹¹ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹² The Feil Family Brain and Mind Research Institute, New York, NY, USA. chm2042@med.cornell.edu.

PMID: 31907405
DOI: 10.1038/s41587-019-0329-2

The therapeutic landscape for cells engineered with chimeric antigen receptors

Matthew MacKay et al. Nat Biotechnol. 2020 Feb.

. 2020 Feb;38(2):233-244.

doi: 10.1038/s41587-019-0329-2. Epub 2020 Jan 6.

Authors

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
² The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.
³ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
⁴ Tri-Institutional Computational Biology and Medicine Program, Weill Cornell Medicine of Cornell University, New York, NY, USA.
⁵ Yale University, New Haven, CT, USA.
⁶ Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
⁷ National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Shenzhen, China. wushixiu@zju.edu.cn.
⁸ Chinese Academy of Medical Science, Peking Union Medical College, Shenzhen, China. wushixiu@zju.edu.cn.
⁹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹⁰ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹¹ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu.
¹² The Feil Family Brain and Mind Research Institute, New York, NY, USA. chm2042@med.cornell.edu.

PMID: 31907405
DOI: 10.1038/s41587-019-0329-2

Abstract

Despite the global rapid increase in the number of clinical trials employing chimeric antigen receptors (CARs), no comprehensive survey of their scope, targets and design exists. In this study, we present an interactive CAR clinical trial database, spanning 64 targets deployed in T cells (CAR-T), natural killer cells (CAR-NK) or mixtures (CAR-NK/T) from over 500 clinical trials in 20 countries, encompassing >20,000 patients. By combining these data with transcriptional and proteomic data, we create a 'targetable landscape' for CAR cell therapies based on 13,206 proteins and RNAs across 78 tissues, 124 cell types and 20 cancer types. These data suggest a landscape of over 100 single targets and over 100,000 target pairs using logical switches for CAR cell engineering. Our analysis of the CAR cellular therapeutic landscape may aid the design of future therapies, improve target-to-patient matching, and ultimately help inform our understanding of CAR therapy's safety and efficacy.

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References

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1. Klebanoff, C. A., Rosenberg, S. A. & Restifo, N. P. Prospects for gene-engineered T cell immunotherapy for solid cancers. Nat. Med. 22, 26–36 (2016). - DOI
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1. Uhlén, M. et al. Proteomics. tissue-based map of the human proteome. Science 347, 1260419 (2015). - DOI
1. Arcangeli, S. et al. Balance of anti-CD123 chimeric antigen receptor binding affinity and density for the targeting of acute myeloid leukemia. Mol. Ther. 25, 1933–1945 (2017). - DOI

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The therapeutic landscape for cells engineered with chimeric antigen receptors

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The therapeutic landscape for cells engineered with chimeric antigen receptors

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