Contributions
Abstract: P893
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) that has demonstrated superior efficacy versus SC IFNB-1a in phase 2 and 3 clinical trials. Alemtuzumab targets CD52, a cell surface protein predominantly expressed on T cells and B cells. Previous reports have shown that alemtuzumab treatment results in rapid depletion, followed by subsequent repopulation of immune cells, for which the kinetics are still to be fully defined. A deeper understanding of the underlying mechanism of action (MOA) of alemtuzumab will facilitate biomarker discovery for potential risk stratification as well as potential treatment effect.
Aims: To investigate the gene expression signatures of peripheral blood mononuclear cells (PBMC) in response to alemtuzumab treatment in patients with RRMS from the CARE-MS I (NCT00530348) and II (NCT00548405) studies.
Methods: Transcriptome analysis was carried out on peripheral blood mononuclear cells (PBMC) from alemtuzumab-treated RRMS patients. Patients were treated with alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. PBMC isolated from whole blood were collected at baseline (pre-alemtuzumab) and Months 12 and 24 post-alemtuzumab initiation, and were analyzed by RNA sequencing methods.
Results: Gene co-expression modules were identified that represent gene signatures of distinct immune cell types. T cell signature expression (i.e., CD4, CD8, and CD3) decreased from baseline to Months 12 and 24, whereas B cell signature expression (i.e., CD19, CD20 and CD79A) increased from baseline to Months 12 and 24. From baseline to Month 24, the inflammatory signature expression significantly decreased in PBMCs. Characterization of immune signatures reflect known changes in constituent cell populations during and after alemtuzumab treatment, and reveal a less inflammatory milieu 1 year after the second course of alemtuzumab.
Conclusion: These results provide insight into the biological effect of treatment at the transcriptional level of immune cells types, in addition to the known effects of alemtuzumab on T and B cells. These insights may aid in further understanding of the MOA of alemtuzumab, and may help inform future biomarker research.
Disclosure: MZ, Y-CC, SS, AJ, JG, KK, and SM: Employees of Sanofi. STUDY SUPPORT: Sanofi.
Abstract: P893
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) that has demonstrated superior efficacy versus SC IFNB-1a in phase 2 and 3 clinical trials. Alemtuzumab targets CD52, a cell surface protein predominantly expressed on T cells and B cells. Previous reports have shown that alemtuzumab treatment results in rapid depletion, followed by subsequent repopulation of immune cells, for which the kinetics are still to be fully defined. A deeper understanding of the underlying mechanism of action (MOA) of alemtuzumab will facilitate biomarker discovery for potential risk stratification as well as potential treatment effect.
Aims: To investigate the gene expression signatures of peripheral blood mononuclear cells (PBMC) in response to alemtuzumab treatment in patients with RRMS from the CARE-MS I (NCT00530348) and II (NCT00548405) studies.
Methods: Transcriptome analysis was carried out on peripheral blood mononuclear cells (PBMC) from alemtuzumab-treated RRMS patients. Patients were treated with alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. PBMC isolated from whole blood were collected at baseline (pre-alemtuzumab) and Months 12 and 24 post-alemtuzumab initiation, and were analyzed by RNA sequencing methods.
Results: Gene co-expression modules were identified that represent gene signatures of distinct immune cell types. T cell signature expression (i.e., CD4, CD8, and CD3) decreased from baseline to Months 12 and 24, whereas B cell signature expression (i.e., CD19, CD20 and CD79A) increased from baseline to Months 12 and 24. From baseline to Month 24, the inflammatory signature expression significantly decreased in PBMCs. Characterization of immune signatures reflect known changes in constituent cell populations during and after alemtuzumab treatment, and reveal a less inflammatory milieu 1 year after the second course of alemtuzumab.
Conclusion: These results provide insight into the biological effect of treatment at the transcriptional level of immune cells types, in addition to the known effects of alemtuzumab on T and B cells. These insights may aid in further understanding of the MOA of alemtuzumab, and may help inform future biomarker research.
Disclosure: MZ, Y-CC, SS, AJ, JG, KK, and SM: Employees of Sanofi. STUDY SUPPORT: Sanofi.