Title:
ANTIGEN-TARGETING, ANTI-CD16A AND IMMUNE EFFECTOR CELL-ACTIVATING TRIFUNCTIONAL FUSION PROTEIN, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/036270
Kind Code:
A1
Abstract:
Disclosed is an antigen-targeting, anti-CD16A and immune effector cell-activating trifunctional fusion protein, which comprises a CD16A binding region that specifically binds to CD16A, a TAA binding region that specifically binds to a tumor-associated antigen (TAA), an IL-15/IL-15 Rα complex formed by means of binding of IL-15 to IL-15 Rα, and an FC domain. The designed tumor-targeting innate immune cell activating molecule, i.e. the anti-TAA, anti-CD16A and cytokine IL15 trifunctional fusion protein, can simultaneously bind to a TAA on a tumor cell and CD16A on an NK cell, thereby making the NK cell target tumors. The NK cell releases perforin and granzyme to induce apoptosis and cause the death of the tumor cells. The cytokine IL15 is expanded to maintain the function of the NK cell, stimulate the proliferation of immune cells, and change the immune microenvironment of the tumor.
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Inventors:
QU XIANGDONG (CN)
PAN QIN (CN)
PAN QIN (CN)
Application Number:
PCT/CN2022/117940
Publication Date:
March 16, 2023
Filing Date:
September 08, 2022
Export Citation:
Assignee:
QURE BIOTECHNOLOGY SHANGHAI CO LTD (CN)
International Classes:
C07K19/00; A61K39/395; A61P35/00; A61P37/02
Foreign References:
| CN113135996A | 2021-07-20 | |||
| CN109153728A | 2019-01-04 | |||
| US20200148737A1 | 2020-05-14 |
Other References:
CHENG, YING: "Construction of Trispecific Antibody and Its Anti-tumor Effect on NK Cell", CHINESE DOCTORAL DISSERTATIONS FULL-TEXT DATABASE, no. 1, 1 September 2020 (2020-09-01), CN, pages 1 - 121, XP009544419, DOI: 10.27517/d.cnki.gzkju.2020.001750
DEMARIA OLIVIER, GAUTHIER LAURENT, DEBROAS GUILHAUME, VIVIER ERIC: "Natural killer cell engagers in cancer immunotherapy: Next generation of immuno‐oncology treatments", EUROPEAN JOURNAL OF IMMUNOLOGY, WILEY-VCH, HOBOKEN, USA, vol. 51, no. 8, 1 August 2021 (2021-08-01), Hoboken, USA, pages 1934 - 1942, XP093029108, ISSN: 0014-2980, DOI: 10.1002/eji.202048953
XU JING, NIU TING: "Natural killer cell-based immunotherapy for acute myeloid leukemia", JOURNAL OF HEMATOLOGY & ONCOLOGY, vol. 13, no. 1, 1 December 2020 (2020-12-01), XP093046654, DOI: 10.1186/s13045-020-00996-x
YI MEI, BO XIANG, JIANBO YANG: "Novel Strategies for Redirecting NK Cells in Cancer Immunotherapy", JOURNAL OF NUTRITIONAL ONCOLOGY, vol. 2, no. 2, 15 May 2017 (2017-05-15), pages 35 - 41, XP093046652
HENGRUI PHARMACEUTICAL, 14 May 2019 (2019-05-14)
"UniProtKB", Database accession no. Q13261
MOL CANCER THER, vol. 11, no. 6, June 2012 (2012-06-01)
DEMARIA OLIVIER, GAUTHIER LAURENT, DEBROAS GUILHAUME, VIVIER ERIC: "Natural killer cell engagers in cancer immunotherapy: Next generation of immuno‐oncology treatments", EUROPEAN JOURNAL OF IMMUNOLOGY, WILEY-VCH, HOBOKEN, USA, vol. 51, no. 8, 1 August 2021 (2021-08-01), Hoboken, USA, pages 1934 - 1942, XP093029108, ISSN: 0014-2980, DOI: 10.1002/eji.202048953
XU JING, NIU TING: "Natural killer cell-based immunotherapy for acute myeloid leukemia", JOURNAL OF HEMATOLOGY & ONCOLOGY, vol. 13, no. 1, 1 December 2020 (2020-12-01), XP093046654, DOI: 10.1186/s13045-020-00996-x
YI MEI, BO XIANG, JIANBO YANG: "Novel Strategies for Redirecting NK Cells in Cancer Immunotherapy", JOURNAL OF NUTRITIONAL ONCOLOGY, vol. 2, no. 2, 15 May 2017 (2017-05-15), pages 35 - 41, XP093046652
HENGRUI PHARMACEUTICAL, 14 May 2019 (2019-05-14)
"UniProtKB", Database accession no. Q13261
MOL CANCER THER, vol. 11, no. 6, June 2012 (2012-06-01)
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