Monoclonal Antibodies in Immunodiagnosis and Immunotherapy最新文献

Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H₂Mab-77 (mouse IgG₁, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cells in vitro and exhibited the potent antitumor activity in vivo. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.

Monoclonal antibodies targeted against SARS-COV-2 have been recruited in the challenging treatment of COVID-19 with few clinically significant side effects. Casivirimab/imdevimab, a combination of monoclonal antibodies targeted against SARS-COV-2 spike protein, was shown to effectively prevent recently infected high-risk COVID-19 patients from developing severe disease. Its efficacy waned with the emergence of the resistant omicron variant in late 2021. We recorded the real-world effect of casivirimab/imdevimab on 116 high-risk COVID-19 patients. Cumulative need for hospitalization, mortality, new-onset disease, and reinfections was monitored. Casivirimab/imdevimab effect was independent from previous immunization. The cohort was further divided into two subgroups: patients infected during a delta variant prevalent period were more likely to become admitted but as likely to die than patients infected with the omicron variant, in support of its protective effect from clinical studies. Cumulative reinfection incidence in treated patients, interestingly, was lower than in the general population.

CC chemokine receptor type-2 (CCR2) is a member of the G protein-coupled receptors, and is mainly expressed on cell surface of immune cells. CCR2 binds to its ligand, C-C motif chemokine 2 (also named as monocyte chemoattractant protein-1), which involves in the tumor progression by modulating the tumor microenvironment. Therefore, the monoclonal antibody (mAb) targeting CCR2 could be one of the strategies for cancer treatment. In this study, we investigated the critical epitope of C₂Mab-6, an anti-mouse CCR2 (mCCR2) mAb developed by N-terminal peptides immunization. We first performed enzyme-linked immunosorbent assay (ELISA) using N-terminal peptides of mCCR2 and demonstrated that C₂Mab-6 recognizes 1-19 amino acids of mCCR2. We further performed ELISA using 20 alanine-substituted peptides of mCCR2. C₂Mab-6 lost the reaction to the alanine-substituted peptides of D3A, N4A, M6A, P8A, Q9A, and F10A. These results indicate that the binding epitope of C₂Mab-6 includes Asp3, Asn4, Met6, Pro8, Gln9, and Phe10 of mCCR2.

CD10 is a cell surface metalloendopeptidase that cleaves and degrades many secreted physiologically active peptides by its enzymatic activity. Although CD10 expression has been found in various types of cells, its expression is increased in several cancers, including renal cancer. In this study, the antitumor activity of a novel anti-human CD10 monoclonal antibody (mAb) was investigated. A defucosylated mouse IgG_2a version of C₁₀Mab-31 (31-mG_2a-f) was created from an anti-CD10 mAb, C₁₀Mab-31 (IgG₁, kappa). Both C₁₀Mab-31 and 31-mG_2a-f specifically reacted with endogenous CD10 in renal cancer cells, VMRC-RCW, with the dissociation constant (K_D) values of 6.3 × 10^-9 M and 1.1 × 10^-9 M, respectively, indicating high binding affinity. To further examine the anti-CD10 mAb-mediated effector functions, the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were examined. The 31-mG_2a-f significantly exhibited ADCC and CDC against VMRC-RCW cells in vitro. Furthermore, 31-mG_2a-f exhibited antitumor activities in mouse xenografts of VMRC-RCW cells. These results suggest that 31-mG_2a-f exerts antitumor activities against CD10-expressing renal cancers and could be a valuable therapeutic candidate for treating them.

The CC chemokine receptor 6 (CCR6) is a G protein-coupled receptor family member that is highly expressed in B lymphocytes, certain subsets of effector and memory T cells, and immature dendritic cells. CCR6 has only one chemokine ligand, CCL20. The CCL20-CCR6 axis has been recognized as a therapeutic target for autoimmune diseases and tumor. This study developed specific monoclonal antibodies (mAbs) against mouse CCR6 (mCCR6) using the peptide immunization method. The established anti-mCCR6 mAb, C₆Mab-13 (rat IgG₁, kappa), reacted with mCCR6-overexpressed Chinese hamster ovary-K1 (CHO/mCCR6), and mCCR6-endogenously expressed P388 (mouse lymphoid neoplasma) and J774-1 (mouse macrophage-like) cells in flow cytometry. The dissociation constant (K_D) of C₆Mab-13 for CHO/mCCR6 cells was determined to be 2.8 × 10^-9 M, indicating that C₆Mab-13 binds to mCCR6 with high affinity. In summary, C₆Mab-13 is useful for detecting mCCR6-expressing cells through flow cytometry.

1F7 is a monoclonal antibody that recognizes an idiotypic determinant expressed on primate antibodies binding to HIV-1 and hepatitis C proteins. This monoclonal antibody was used as a tool to dissect the immune response in humans infected with HIV-1 and hepatitis B. Furthermore, 1F7 was also used to manipulate the immune response against HIV-1 in macaques. The generation of a monoclonal antibody describing a network suggests similar antibodies could be developed as tools to dissect entangled networks in autoimmune diseases and allergic reactions. This review discusses the body of work done with 1F7 in the light of contemporary immunology.

It has been widely accepted that monoclonal antibody (mAb) is an effective tool for cancer immunotherapy. The C-C motif chemokine receptor 8 (CCR8) is highly expressed in regulatory T cells and many cancers and is associated with the progression of the cancers. However, its role in cancer progression remains unclear. Thus, the development of mAbs for CCR8 leads to cancer immunotherapy and elucidation of unknown mechanisms of CCR8-dependent cancer progression. In this study, we have developed an anti-mouse CCR8 (mCCR8) mAb (clone C₈Mab-1, rat IgG_2a, kappa) using the Cell-Based Immunization and Screening (CBIS) method. We showed that C₈Mab-1 and its recombinant antibody (recC₈Mab-1) bind to mCCR8-overexpressed Chinese hamster ovary (CHO)-K1 cells (CHO/mCCR8), but not to the parental CHO-K1 cells, in flow cytometry and immunofluorescence. Moreover, C₈Mab-1 and recC₈Mab-1 specifically reacted to P388 (a mouse lymphocyte-like cells) and J774-1 (a mouse macrophage-like cells), which express endogenous mCCR8, in both applications. These results suggest that C₈Mab-1, developed using the CBIS method, is useful for flow cytometry and immunocytochemistry against exogenous and endogenous mCCR8.