دورية أكاديمية
CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma.
| العنوان: | CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma. |
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| المؤلفون: | Chen X; Virtuoso Therapeutics, Inc., San Mateo, California., Wong OK; Virtuoso Therapeutics, Inc., San Mateo, California., Reiman L; Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Sherbenou DW; Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado., Post L; Virtuoso Therapeutics, Inc., San Mateo, California. |
| المصدر: | Molecular cancer therapeutics [Mol Cancer Ther] 2024 Feb 01; Vol. 23 (2), pp. 127-138. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research, Inc Country of Publication: United States NLM ID: 101132535 Publication Model: Print Cited Medium: Internet ISSN: 1538-8514 (Electronic) Linking ISSN: 15357163 NLM ISO Abbreviation: Mol Cancer Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001- |
| مواضيع طبية MeSH: | Antibodies, Bispecific*/pharmacology , Antibodies, Bispecific*/therapeutic use , Lymphoma* , Multiple Myeloma*/pathology, Humans ; ADP-ribosyl Cyclase 1/metabolism ; Cell Line, Tumor ; Intercellular Adhesion Molecule-1/metabolism |
| مستخلص: | The cluster of differentiation 38 (CD38) is a well-validated target for treating multiple myeloma. Although anti-CD38 mAbs have demonstrated outstanding initial responses in patients with multiple myeloma, nearly all patients eventually develop resistance and relapse. In addition, currently approved CD38 targeting therapies have failed to show monotherapy efficacy in lymphomas, where CD38 expression is present but at lower levels. To effectively target CD38 on tumor cells, we generated an antibody-dependent cellular cytotoxicity (ADCC) enhanced bispecific CD38 x intercellular cell adhesion molecule 1 (ICAM-1) antibody, VP301. This bispecific antibody targets unique epitopes on CD38 and ICAM-1 on tumor cells with reduced red blood cell binding compared with the benchmark CD38 antibody daratumumab. VP301 demonstrated potent ADCC and antibody-dependent cellular phagocytosis activities on a selected set of myeloma and lymphoma cell lines even those with low CD38 expression. In an ex vivo drug sensitivity assay, we observed responses to VP301 in multiple myeloma primary samples from relapsed/refractory patients. Moreover, VP301 demonstrated potent tumor inhibition activities in in vivo myeloma and lymphoma models. Interestingly, combination of VP301 with the immunomodulatory drug, lenalidomide, led to synergistic antitumor growth activity in an in vivo efficacy study. In conclusion, the CD38 x ICAM-1 bispecific antibody VP301 demonstrated promising efficacy and specificity toward CD38+ and ICAM-1+ tumor cells and represents a novel approach for treating multiple myeloma and lymphoma. (©2023 American Association for Cancer Research.) |
| معلومات مُعتمدة: | n/a |
| المشرفين على المادة: | EC 3.2.2.6 (ADP-ribosyl Cyclase 1) 0 (Antibodies, Bispecific) 126547-89-5 (Intercellular Adhesion Molecule-1) |
| تواريخ الأحداث: | Date Created: 20231010 Date Completed: 20240205 Latest Revision: 20240205 |
| رمز التحديث: | 20240206 |
| DOI: | 10.1158/1535-7163.MCT-23-0052 |
| PMID: | 37816503 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-8514 |
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| DOI: | 10.1158/1535-7163.MCT-23-0052 |