作者: Inderberg, Else Marit ; Graczyk-Jarzynka, Agnieszka ; Granica, Monika ; Domagala, Joanna ; Majchrzak, Martyna ; Dostalova, Lenka ; Firczuk, Malgorzata ; Forcados, Christopher ; Marhelava, Katsiaryna ; Poreba, Marcin ; Barankiewicz, Joanna ; Zhylko, Andriy ; Gehlert, Carina Lynn ; Fidyt, Klaudyna ; Kusowska, Aleksandra ; Krawczyk, Marta ; Peipp, Matthias ; Bobrowicz, Malgorzata ; Szumera-Cieckiewicz, Anna ; Baranowska, Iwona ; Winiarska, Magdalena ; Slusarczyk, Aleksander ; Wälchli, Sébastien ; Šmída, Michal ; Prochorec-Sobieszek, Monika ; Pepek, Monika ; Kubacz, Matylda

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

1993-02-01·The Journal of Biochemistry4区 · 生物学

Detection of Subtle Differences in the Surface Structure of Lysozymes by Use of an Immobilized Fab Fragment

4区 · 生物学

Article

作者: Keiichl Kawano ; Taiji Imoto ; Hiroshi Tsuji ; Tadashi Ueda ; Yasunori Yamaguchi ; Yoshito Abe ; Kenji Akasaki ; Hidenori Yamada

A method was developed to evaluate the association constant at physiological pH (pH 7.5) between a lysozyme and the Fab fragment derived from anti-lysozyme monoclonal antibody 37-7, which was immobilized to the adsorbent for HPLC. Comparison of the association constants between lysozymes and the immobilized Fab fragment indicated that mAb 37-7 recognized the prominently exposed regions (hills and ridges) around His15 of hen lysozyme, but His15 itself was not directly involved in the binding with mAb 37-7. Moreover, the epitope was confirmed by the reactivity of His15 with monoiodoacetic acid in the presence of mAb 37-7. The association constant of 15-carboxymethylated histidine lysozyme (15CM lysozyme) with the immobilized Fab fragment was smaller by one-seventh than that of 15-carboxamidated histidine lysozyme, though the side chains introduced were almost identical in size. From the pH titration of 15CM lysozyme with 13C-enriched carboxyl group by use of 13C-NMR, the pKa of the introduced carboxyl group was evaluated to be 5.06. Since the carboxyl group was fully ionized under the conditions of measurement (pH 7.5), electrostatic repulsion was found to disturb severely the association between mAb 37-7 and hen lysozyme. Moreover, it was demonstrated that, because of the high reproducibility of measurement, the immobilized Fab fragment could detect subtle differences in the surface structure of lysozymes.

1989-02-01·European Journal of Immunology3区 · 医学

Alternative molecular form of human T cell‐specific antigen CD27 expressed upon T cell activation

3区 · 医学

Article

作者: E. De Vries ; C. J. M. Melief ; C. Sluyser ; H. Klein ; R. A. W. Van Lier ; J. Borst

AbstractThe CD27 membrane antigen is exclusively present on a large subset of human peripheral blood T lymphocytes and on mature thymocytes. Several observations point towards a specific role of this molecule on activated T cells. Upon T cell activation induced via the T cell receptor complex, CD27 expression greatly increases, while addition of anti‐CD27 monoclonal antibodies amplifies the proliferative response. Within the CD4 subset, only CD27 T cells provide helper activity for B cell differentiation. Interestingly, CD27 expression differs not only quantitatively, but also qualitatively between resting and activated T cells. On resting cells, CD27 is a disulfide‐linked homodimer with subunits of 55 kDa molecular mass. Upon activation, also a 55‐kDa monomer seems to occur, while in addition a 32‐kDa component is found. The relationship between these two proteins has been investigated. The 55‐kDa and 32‐kDa molecules do not seem to be physically associated. The two CD27 components are structurally highly homologous as determined by two‐dimensional mapping of tryptic peptides. They both express the epitopes recognized by anti‐CD27 antibodies, indicating that the 32‐kDa molecule is also T cell specific. Both 55‐kDa and 32‐kDa molecules carry N‐linked carbohydrate groups. However, they differ in other, not yet specified, post‐translational modifications, and do not arise from a common precursor simply by alternative N‐glycosylation. The 32‐kDa form may be derived by proteolytic processing from the 55‐kDa protein, but most likely not from a larger (common) precursor. Alternatively, both molecules may arise from a common gene by alternative mRNA splicing, or be derived from highly homologous genes. The dramatic change in molecular composition of CD27 suggests a newly acquired function for CD27 on activated T cells.

100 项与 Anti-CD27 monoclonal antibody(Aduro BioTech, Inc.) 相关的药物交易

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