Antibody combinations for treating cancer in specific patients
A technology for patients and cancer, applied in the direction of antibodies, specific peptides, drug combinations, etc., can solve problems such as unclear and reduced antibody efficacy
Pending Publication Date: 2022-03-01
BIOINVENT INT AB +1
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However, in contrast to Dahan et al., using blocking antibodies against Fcγ receptors alone, the authors identified activating mouse Fcγ receptor III and inhibitory mouse Fcγ receptor II as potential reasons for the reduced efficacy of anti-PD-1 antibodies
Therefore, the relative importance of (individual) activating and inhibitory Fcγ receptors as potential causes of reduced efficacy of anti-PD-1 antibodies, how they limit the efficacy of clinically relevant human anti-PD-1 antibodies, or which activating or inhibitory Fcγ receptors Inhibitory FcγR should be blocked to enhance anti-PD-1 antibody activity, not clear from prior art
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[0038] Here, we demonstrate that only anti-FcγRIIB antibodies with good Fc:FcγR binding, but not with impaired Fc:FcγR binding, can enhance the therapeutic efficacy of anti-PD-1 antibodies in vivo and prevent the disease caused by clinically relevant human anti-PD-1 antibodies. In vitro phagocytosis of PD-1 overexpressing T cells. This finding is novel and unexpected, as the aforementioned reference studies on the role of FcγRs in anti-PD-1 therapy demonstrated a broad role for activating FcγRs compared to inhibitory FcγRs (Dahan, R. et al. 2015) "cancer cell" 28(3):285-295), or separate activating (FcγRIII) and inhibitory FcγRIIB as potential causes of impaired anti-PD-1 antibody activity (Arlauckas, S.P. et al. (2017) "Science Translational Medicine" 9(389)).
[0039] In light of some of the inventors' earlier findings related to antibodies against other immune checkpoints, including anti-CTLA-4 in particular, where only anti-FcγRIIB antibodies with impaired Fc:FcγR bind...
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The combined use of a first antibody molecule that specifically binds to Fc [gamma] RIIb through its Fab region and binds to Fc [gamma] receptor through its Fc region and a second antibody molecule that specifically binds to PD-1 and binds to at least one Fc [gamma] receptor through its Fc region in the treatment of cancer in a patient having tumor-infiltrating T lymphocytes having medium or high PD-1 expression is described, as well as pharmaceutical compositions and kits comprising these two antibody molecules, as well as methods of using these two antibodies to treat cancer. A diagnostic test for identifying patients who benefit from the treatment described herein is also described.
Description
technical field [0001] The present invention relates to 1) a first antibody molecule that specifically binds FcγRIIb through its Fab region and Fcγ receptor through its Fc region, and 2) specifically binds PD-1 and binds at least one Fcγ receptor through its Fc region Combination use of a second antibody molecule in the treatment of cancer in a patient with moderate or high PD-1 expression on CD3 positive tumor infiltrating lymphocytes (TILs). Background technique [0002] Immunosuppressive checkpoint receptors, such as CTLA-4 or PD-1 (also denoted PD1), are cell surface receptors that interact with their ligand receptors (such as B7 family members CD80 and CD86, respectively, and PD-L1) When bound, it transmits inhibitory signals into the interior of the cell, thereby limiting cell activation and proliferation, preventing excessive inflammation and helping to maintain self-tolerance. Animals with genetic defects in such inhibitory immune checkpoints are associated with exa...
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IPC IPC(8): C07K16/28A61K39/395A61P35/00
CPCC07K16/283C07K16/2818A61P35/00A61K2039/507C07K2317/56C07K2317/565C07K2317/76C07K16/2827C07K16/2866C07K16/2887C07K2317/526G01N33/574C07K2317/55
Inventor B·弗伦德修斯英格丽德·泰格L·玛藤松I·卡尔松马克·克拉格斯蒂芬·贝尔斯R·奥尔德姆
Owner BIOINVENT INT AB