Bispecific dendritic-T cell engager potentiates anti-tumor immunity

Yuval Shapir Itai; Oren Barboy; Ran Salomon; Akhiad Bercovich; Ken Xie; Eitan Winter; Tamar Shami; Ziv Porat; Neta Erez; Amos Tanay; Ido Amit; Rony Dahan

doi:10.1016/j.cell.2023.12.011

Bispecific dendritic-T cell engager potentiates anti-tumor immunity

Yuval Shapir Itai, Oren Barboy, Ran Salomon, Akhiad Bercovich, Ken Xie, Eitan Winter, Tamar Shami, Ziv Porat, Neta Erez, Amos Tanay, Ido Amit^*, Rony Dahan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promising cancer immunotherapy approach. However, its effect on tumor immunity is narrow, as most patients do not respond to the treatment or suffer from recurrence. We show that the crosstalk between conventional type I dendritic cells (cDC1) and T cells is essential for an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a bispecific DC-T cell engager (BiCE), a reagent that facilitates physical interactions between PD-1⁺ T cells and cDC1. BiCE treatment promotes the formation of active dendritic/T cell crosstalk in the tumor and tumor-draining lymph nodes. In vivo, single-cell and physical interacting cell analysis demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.

Original language	English
Pages (from-to)	375-389.e18
Journal	Cell
Volume	187
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2023.12.011
Publication status	Published - 18 Jan 2024

Bibliographical note

We'd like to thank Genia Brodsky from the Scientific Illustration unit of the Weizmann Institute for her artwork. R.D. is an incumbent of the Rina Gudinski Career Development Chair, funded by the European Research Council, Israel Cancer Association, Israel Science Foundation, Moross Integrated Cancer Center, Flight Attendant Medical Research Institute, Dwek Institute for Cancer Therapy Research, Teva Pharmaceuticals, Center for Immunotherapy at the Weizmann Institute of Science, David E. Stone and Sheri Hirschfield Stone 75th Anniversary Fund, Rising Tide Foundation, Miel de Botton, Garvan-Weizmann Partnership donors, and Elie Hirschfeld and Dr. Sarah Schlesinger. I.A. holds the Eden and Steven Romick Professorial Chair, and supported by the HHMI International Scholar Award, European Union (no. 101055341-TROJAN-Cell); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) –, Israel Science Foundation, Helen and Martin Kimmel awards for innovative investigation, ISF Israel Precision Medicine Program (IPMP), Dwek Institute for Cancer Therapy research grant, Moross Integrated Canceer Center grant, Ekard Institue for Cancer Diagnosis Research, Morris Kahn Institute for Human Immunology, Swiss Society Institute for Cancer Prevention research, Elsie and Marvin Dekelboum Family Foundation, Lotte and John Hecht Memorial Foundation, Schwartz Reisman Collaborative Science Program, and Betty Kahn Foundation. N.E. is supported by the Melanoma Research Alliance (award ID 826222), and the Israel Science Foundation Personalized Medicine Program (IPMP no. 3495/19).

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2023.12.011

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title = "Bispecific dendritic-T cell engager potentiates anti-tumor immunity",

abstract = "Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promising cancer immunotherapy approach. However, its effect on tumor immunity is narrow, as most patients do not respond to the treatment or suffer from recurrence. We show that the crosstalk between conventional type I dendritic cells (cDC1) and T cells is essential for an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a bispecific DC-T cell engager (BiCE), a reagent that facilitates physical interactions between PD-1+ T cells and cDC1. BiCE treatment promotes the formation of active dendritic/T cell crosstalk in the tumor and tumor-draining lymph nodes. In vivo, single-cell and physical interacting cell analysis demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.",

author = "{Shapir Itai}, Yuval and Oren Barboy and Ran Salomon and Akhiad Bercovich and Ken Xie and Eitan Winter and Tamar Shami and Ziv Porat and Neta Erez and Amos Tanay and Ido Amit and Rony Dahan",

note = "We'd like to thank Genia Brodsky from the Scientific Illustration unit of the Weizmann Institute for her artwork. R.D. is an incumbent of the Rina Gudinski Career Development Chair, funded by the European Research Council, Israel Cancer Association, Israel Science Foundation, Moross Integrated Cancer Center, Flight Attendant Medical Research Institute, Dwek Institute for Cancer Therapy Research, Teva Pharmaceuticals, Center for Immunotherapy at the Weizmann Institute of Science, David E. Stone and Sheri Hirschfield Stone 75th Anniversary Fund, Rising Tide Foundation, Miel de Botton, Garvan-Weizmann Partnership donors, and Elie Hirschfeld and Dr. Sarah Schlesinger. I.A. holds the Eden and Steven Romick Professorial Chair, and supported by the HHMI International Scholar Award, European Union (no. 101055341-TROJAN-Cell); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) –, Israel Science Foundation, Helen and Martin Kimmel awards for innovative investigation, ISF Israel Precision Medicine Program (IPMP), Dwek Institute for Cancer Therapy research grant, Moross Integrated Canceer Center grant, Ekard Institue for Cancer Diagnosis Research, Morris Kahn Institute for Human Immunology, Swiss Society Institute for Cancer Prevention research, Elsie and Marvin Dekelboum Family Foundation, Lotte and John Hecht Memorial Foundation, Schwartz Reisman Collaborative Science Program, and Betty Kahn Foundation. N.E. is supported by the Melanoma Research Alliance (award ID 826222), and the Israel Science Foundation Personalized Medicine Program (IPMP no. 3495/19).",

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doi = "10.1016/j.cell.2023.12.011",

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AU - Shapir Itai, Yuval

AU - Barboy, Oren

AU - Salomon, Ran

AU - Bercovich, Akhiad

AU - Xie, Ken

AU - Winter, Eitan

AU - Shami, Tamar

AU - Porat, Ziv

AU - Erez, Neta

AU - Tanay, Amos

AU - Amit, Ido

AU - Dahan, Rony

N1 - We'd like to thank Genia Brodsky from the Scientific Illustration unit of the Weizmann Institute for her artwork. R.D. is an incumbent of the Rina Gudinski Career Development Chair, funded by the European Research Council, Israel Cancer Association, Israel Science Foundation, Moross Integrated Cancer Center, Flight Attendant Medical Research Institute, Dwek Institute for Cancer Therapy Research, Teva Pharmaceuticals, Center for Immunotherapy at the Weizmann Institute of Science, David E. Stone and Sheri Hirschfield Stone 75th Anniversary Fund, Rising Tide Foundation, Miel de Botton, Garvan-Weizmann Partnership donors, and Elie Hirschfeld and Dr. Sarah Schlesinger. I.A. holds the Eden and Steven Romick Professorial Chair, and supported by the HHMI International Scholar Award, European Union (no. 101055341-TROJAN-Cell); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) –, Israel Science Foundation, Helen and Martin Kimmel awards for innovative investigation, ISF Israel Precision Medicine Program (IPMP), Dwek Institute for Cancer Therapy research grant, Moross Integrated Canceer Center grant, Ekard Institue for Cancer Diagnosis Research, Morris Kahn Institute for Human Immunology, Swiss Society Institute for Cancer Prevention research, Elsie and Marvin Dekelboum Family Foundation, Lotte and John Hecht Memorial Foundation, Schwartz Reisman Collaborative Science Program, and Betty Kahn Foundation. N.E. is supported by the Melanoma Research Alliance (award ID 826222), and the Israel Science Foundation Personalized Medicine Program (IPMP no. 3495/19).

PY - 2024/1/18

Y1 - 2024/1/18

N2 - Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promising cancer immunotherapy approach. However, its effect on tumor immunity is narrow, as most patients do not respond to the treatment or suffer from recurrence. We show that the crosstalk between conventional type I dendritic cells (cDC1) and T cells is essential for an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a bispecific DC-T cell engager (BiCE), a reagent that facilitates physical interactions between PD-1+ T cells and cDC1. BiCE treatment promotes the formation of active dendritic/T cell crosstalk in the tumor and tumor-draining lymph nodes. In vivo, single-cell and physical interacting cell analysis demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.

AB - Immune checkpoint inhibition treatment using aPD-1 monoclonal antibodies is a promising cancer immunotherapy approach. However, its effect on tumor immunity is narrow, as most patients do not respond to the treatment or suffer from recurrence. We show that the crosstalk between conventional type I dendritic cells (cDC1) and T cells is essential for an effective aPD-1-mediated anti-tumor response. Accordingly, we developed a bispecific DC-T cell engager (BiCE), a reagent that facilitates physical interactions between PD-1+ T cells and cDC1. BiCE treatment promotes the formation of active dendritic/T cell crosstalk in the tumor and tumor-draining lymph nodes. In vivo, single-cell and physical interacting cell analysis demonstrates the distinct and superior immune reprogramming of the tumors and tumor-draining lymph nodes treated with BiCE as compared to conventional aPD-1 treatment. By bridging immune cells, BiCE potentiates cell circuits and communication pathways needed for effective anti-tumor immunity.

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DO - 10.1016/j.cell.2023.12.011

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AN - SCOPUS:85182569575

SN - 0092-8674

VL - 187

SP - 375-389.e18

JO - Cell

JF - Cell

IS - 2

ER -

Bispecific dendritic-T cell engager potentiates anti-tumor immunity

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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