BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression

BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression

BackgroundCancer immunotherapy has revolutionized cancer treatment. However, considering the limited success of immunotherapy to only some cancer types and patient cohorts, there is an unmet need for developing new treatments that will result in higher response rates in patients with cancer. Immunog...

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Bibliographic Details
Published in:Journal for immunotherapy of cancer Vol. 10; no. 9; p. e004859
Main Authors: Mandel, Ilana, Haves Ziv, Dana, Goldshtein, Ilana, Peretz, Tsuri, Alishekevitz, Dror, Fridman Dror, Anna, Hakim, Motti, Hashmueli, Sharon, Friedman, Itay, Sapir, Yair, Greco, Rita, Qu, Hongjing, Nestle, Frank, Wiederschain, Dmitri, Pao, Lily, Sharma, Sharad, Ben Moshe, Tehila
Format: Journal Article
Language:English
Published: London BMJ Publishing Group Ltd 01-09-2022
BMJ Publishing Group LTD
BMJ Publishing Group
Series:Original research
Subjects:
Age
Blood banks
Clinical/Translational Cancer Immunotherapy
Colorectal cancer
Cytokines
Cytotoxicity
Immunotherapy
Kidney cancer
Lung cancer
Lymphocyte Activation
Lymphocytes
Macrophages
Melanoma
Monoclonal antibodies
Translational Medical Research
Tumor Escape
Tumors
United States > US
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Summary:BackgroundCancer immunotherapy has revolutionized cancer treatment. However, considering the limited success of immunotherapy to only some cancer types and patient cohorts, there is an unmet need for developing new treatments that will result in higher response rates in patients with cancer. Immunoglobulin-like transcript 2 (ILT2), a LILRB family member, is an inhibitory receptor expressed on a variety of immune cells including T cells, natural killer (NK) cells and different myeloid cells. In the tumor microenvironment, binding of class I MHC (in particular HLA-G) to ILT2 on immune cells mediates a strong inhibitory effect, which manifests in inhibition of antitumor cytotoxicity of T and NK cells, and prevention of phagocytosis of the tumor cells by macrophages.MethodsWe describe here the development and characteristics of BND-22, a novel, humanized monoclonal antibody that selectively binds to ILT2 and blocks its interaction with classical MHC I and HLA-G. BND-22 was evaluated for its binding and blocking characteristics as well as its ability to increase the antitumor activity of macrophages, T cells and NK cells in various in vitro, ex vivo and in vivo systems.ResultsCollectively, our data suggest that BND-22 enhances activity of both innate and adaptive immune cells, thus generating robust and comprehensive antitumor immunity. In humanized mice models, blocking ILT2 with BND-22 decreased the growth of human tumors, hindered metastatic spread to the lungs, and prolonged survival of the tumor-bearing mice. In addition, BND-22 improved the antitumor immune response of approved therapies such as anti-PD-1 or anti-EGFR antibodies.ConclusionsBND-22 is a first-in-human ILT2 blocking antibody which has demonstrated efficient antitumor activity in various preclinical models as well as a favorable safety profile. Clinical evaluation of BND-22 as a monotherapy or in combination with other therapeutics is under way in patients with cancer.Trial registration numberNCT04717375.
Bibliography:Original research
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Present affiliation: The present affiliation of Hongjing Qu is: Affini-T therapeutics, MA, Watertown, USA
SS and TBM are joint senior authors.
Present affiliation: The present affiliation of Dmitri Wiederschain is: Jounce Therapeutics, MA, Cambridge, USA
ISSN:2051-1426
2051-1426
DOI:10.1136/jitc-2022-004859