APX005M, a CD40 agonist antibody with unique epitope specificity and Fc receptor binding profile for optimal therapeutic application

Targeting CD40 with agonist antibodies is a promising approach to cancer immunotherapy. CD40 acts as a master regulator of immunity by mobilizing multiple arms of the immune system to initiate highly effective CD8 + T-cell-mediated responses against foreign pathogens and tumors. The clinical develop...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2021-07, Vol.70 (7), p.1853-1865
Main Authors: Filbert, Erin L., Björck, Pia K., Srivastava, Minu K., Bahjat, Frances R., Yang, Xiaodong
Format: Article
Language:English
Subjects:
Agonists
Animals
Antibodies
Antibodies, Monoclonal - pharmacology
Antibody-Dependent Cell Cytotoxicity
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - pathology
Binding sites
Cancer immunotherapy
Cancer Research
CD40 antigen
CD40 Antigens - agonists
CD40 Antigens - immunology
CD8 antigen
CD8-Positive T-Lymphocytes
Cytotoxicity
Epitopes
Epitopes - immunology
Epitopes - metabolism
Fc receptors
Female
Humans
Immune response
Immunoglobulin G - immunology
Immunology
Immunotherapy
Lymphocytes T
Macaca fascicularis
Male
Medicine
Medicine & Public Health
Oncology
Original
Original Article
Receptors, Fc - metabolism
Tumors
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Description
Summary:Targeting CD40 with agonist antibodies is a promising approach to cancer immunotherapy. CD40 acts as a master regulator of immunity by mobilizing multiple arms of the immune system to initiate highly effective CD8 + T-cell-mediated responses against foreign pathogens and tumors. The clinical development of CD40 agonist antibodies requires careful optimization of the antibody to maximize therapeutic efficacy while minimizing adverse effects. Both epitope specificity and isotype are critical for CD40 agonist antibody mechanism of action and potency. We developed a novel antibody, APX005M, which binds with high affinity to the CD40 ligand-binding site on CD40 and is optimized for selective interaction with Fcγ receptors to enhance agonistic potency while limiting less desirable Fc-effector functions like antibody-dependent cellular cytotoxicity of CD40-expressing immune cells. APX005M is a highly potent inducer of innate and adaptive immune effector responses and represents a promising CD40 agonist antibody for induction of an effective anti-tumor immune response with a favorable safety profile.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-020-02814-2