Structural Surfaceomics Reveals an AML-Specific Conformation of Integrin-β2 As an Immunotherapeutic Target

Mandal, Kunal Kumar; Wicaksono, Gianina; Yu, Clinton; Adams, Jarrett; Hoopmann, Michael R.; Temple, William C; Escobar, Bonell Patiño; Gorelik, Maryna; Ihling, Christian; Nix, Matthew A.; Naik, Akul; Ramos, Emilio; Kasap, Corynn; Steri, Veronica; Serrano, Juan Antonio Camara; Salangsang, Fernando; Phojanakong, Paul; McMillan, Melanie; Gavallos, Victor; Leavitt, Andrew D.; Sinz, Andrea; Huang, Benjamin J.; Stieglitz, Elliot; Smith, Catherine C.; Moritz, Robert L.; Sidhu, Sachdeva S; Huang, Lan; Wiita, Arun P.

doi:10.1182/blood-2022-162697

Cited by 3 publications

(4 citation statements)

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“…While this review is not going to answer this question, it is helpful to acknowledge that integrins are not redundant but may have distinct roles even in the same leukaemia subtype (Gang et al, 2020; Hsieh, Gang, et al, 2013; Ruan et al, 2022). While some integrins are expressed both in solid tumours and AML, only solid tumours have been prominently targeted with CAR T‐cell therapy, but new studies evaluating CAR T‐cell‐based therapies targeting AML antigens are on the way (Marofi et al, 2021) and integrins including integrin β2 are evaluated as a potential targets in CAR T‐cell therapy (Mandal et al, 2022). This new development may bring new approaches to AML therapy.…”

Section: Integrin‐targeted Therapy In Preclinical Evaluation In Solid...mentioning

confidence: 99%

“…Activated conformation specific antibodies were selected by phage display and were incorporated into anti‐β2 CAR T‐cells. The anti‐β2 CAR T‐cell therapy showed cytotoxicity to AML cells in vitro and in mouse PDX models (Mandal et al, 2022).…”

Section: Integrin‐targeted Therapy In Preclinical Evaluation In Amlmentioning

confidence: 99%

“…Activated conformation specific antibodies were selected by phage display and were incorporated into anti-β2 CAR T-cells. The anti-β2 CAR T-cell therapy showed cytotoxicity to AML cells in vitro and in mouse PDX models(Mandal et al, 2022) Sudha et al (2021). have shown that a thyrointegrin αVβ3 antagonist, polyethylene glycol-conjugated bi-triazole tetraiodothyroacetic acid (P-bi-TAT), is an anticancer compound and has high affinity for αvβ3.…”

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confidence: 99%

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Targeting integrins in drug‐resistant acute myeloid leukaemia

Ogana

Hurwitz

Wei

et al. 2023

British J Pharmacology

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Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that interact with not only normal haematopoietic stem cells (HSC) but also leukaemia cells like AML. There are many adhesion molecules in the BM microenvironment; therein, integrins have been of central interest. AML cells express integrins that bind to ligands in the microenvironment, enabling adhesion of leukaemia cells in the microenvironment, thereby initiating intracellular signalling pathways that are associated with cell migration, cell proliferation, survival, and drug resistance that has been described to mediate cell adhesion‐mediated drug resistance (CAM‐DR). Identifying and targeting integrins in AML to interrupt interactions with the microenvironment have been pursued as a strategy to overcome CAM‐DR. Here, we focus on the BM microenvironment and review the role of integrins in CAM‐DR of AML and discuss integrin‐targeting strategies.

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Section: Integrin‐targeted Therapy In Preclinical Evaluation In Solid...mentioning

confidence: 99%

Section: Integrin‐targeted Therapy In Preclinical Evaluation In Amlmentioning

confidence: 99%

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confidence: 99%

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Targeting integrins in drug‐resistant acute myeloid leukaemia

Ogana

Hurwitz

Wei

et al. 2023

British J Pharmacology

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“…First, the search continues for an AML-specific antigen that would mitigate off-tumor toxicity. Large-scale, unbiased investigations of the AML plasma membrane proteome (termed "surfaceome") are underway [134], as is the related field of structural surfaceomics, which searches for specific leukemia-only conformations of surface antigen that may be druggable [135].…”

Section: Future Directionsmentioning

confidence: 99%

Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies

Chen,

Garcia

2023

Acta Haematol

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Background: In the past decade, there have been significant breakthroughs in immunotherapies for B-cell lymphoid malignancies and multiple myeloma, but progress has been much less for acute myeloid leukemia (AML). Nevertheless, challenge begets innovation and several therapeutic strategies are under investigation. Summary: In this review, we review the state of the art in AML immunotherapy including CD33- and CD123-targeted agents, immune checkpoint inhibition, and adoptive cell therapy strategies. We also share conceptual frameworks for approaching the growing catalog of investigational AML immunotherapies and propose future directions for the field. Key Messages: Immunotherapies for AML face significant challenges but novel strategies are in development.

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Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia

Cummins

Gill

2023

Hematology/Oncology Clinics of North America

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Structural Surfaceomics Reveals an AML-Specific Conformation of Integrin-β2 As an Immunotherapeutic Target

Cited by 3 publications

References 0 publications

Targeting integrins in drug‐resistant acute myeloid leukaemia

Targeting integrins in drug‐resistant acute myeloid leukaemia

Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia

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