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ResearchIn-Press PreviewOncology Open Access | 10.1172/JCI189920

CAR-T cells targeting CD155 reduce tumor burden in preclinical models of leukemia and solid tumors

Tianchen Xiong,1 Ge Wang,1 Peng Yu,2 Zhenlong Li,1 Debao Li,2 Jianying Zhang,3 Song Lu,2 Ruiqi Yang,2 Xiaolong Lian,2 Jianhong Mi,2 Rui Ma,1 Zhiyao Li,1 Guido Marcucci,4 Tingting Zhao,2 Michael A. Caligiuri,1 and Jianhua Yu5

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Xiong, T. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Wang, G. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Yu, P. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

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1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

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1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

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1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Lu, S. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

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1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

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1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Mi, J. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Ma, R. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Li, Z. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Marcucci, G. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Zhao, T. in: PubMed | Google Scholar

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Caligiuri, M. in: PubMed | Google Scholar |

1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, United States of America

2Chongqing International Institute for Immunology, Chongqing, China

3Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, United States of America

4Gehr Family Center for Leukemia Research, Hematologic Malignancies Research, City of Hope National Medical Center, Los Angeles, United States of America

5Division of Hematology & Oncology, Department of Medicine, UC Irvine, Irvine, United States of America

Find articles by Yu, J. in: PubMed | Google Scholar

Published June 6, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI189920.
Copyright © 2025, Xiong et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 6, 2025 - Version history
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Abstract

CAR-T cells are a powerful yet expensive tool in cancer immunotherapy. While their use in targeting hematological malignancies is well-established, using a single CAR-T cell therapy to treat both hematological and solid tumors, which can reduce cost, remains largely unexplored. In this study, we identified CD155, an adhesion molecule that is upregulated during tumor progression, as a target for CAR-T cell therapy in both leukemia and solid tumors. We engineered CAR-T cells using human and mouse anti-CD155 antibodies generated from a Berkeley Lights' Beacon platform. These CAR-T cells demonstrated potent anti-tumor activity, significantly reducing tumor burden in preclinical models of acute myeloid leukemia (AML), non-small cell lung cancer (NSCLC), and pancreatic cancer. To reduce potential allogeneic rejection, we generated CAR-T cells using humanized anti-CD155 antibody sequences that retained efficacy. Additionally, murine CAR-T cells targeting mouse CD155 exhibited limited toxic side effects in immunocompetent mice, highlighting the favorable safety profile of this therapy. These findings suggest that CD155 can be targeted by CD155 CAR-T cells safely and effectively, representing an innovative cellular therapeutic strategy that has the potential to expand its scope across both AML and multiple solid tumors, thereby lowering the cost of cellular immunotherapy, especially as allogenic, universal and off-the-shelf CAR-T cell therapies advance to the clinic.

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