Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06435897
Status:
RECRUITING
Last Update Posted:
2024-05-30
First Post:
2024-05-20
Brief Title:
Autoimmune Disease Treatment With Mesenchymal Stem Cells MSCs and CAR-T Cells
Sponsor:
Shenzhen Geno-Immune Medical Institute
Organization:
Shenzhen Geno-Immune Medical Institute
Study Overview
Official Title:
Management of Autoimmune Conditions With Mesenchymal Stem Cells MSCs and CAR-T Cells
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to assess the feasibility safety and efficacy of mesenchymal stem cells MSCs in combination with CAR-T cells in treating autoimmune disease Another goal of the study is to learn more about the safety and function of the MSCs combined with CAR-T cells and their long term effects in autoimmune disease patients
Detailed Description:
Autoimmune disease refers to the disease in which the immune system reacts to the hosts own body and causes damage to tissues and organs At present the pathogenesis of various autoimmune diseases is still not well understood but an imbalanced immune tolerance plays a key role in this process
An ideal therapy to autoimmune disease should eradicate pathogenic autoimmune cells but retain the protective immunity The chimeric antigen receptor-modified T CAR-T cell technology has proven to be highly effective in targeting B cell malignancies and the treatment-induced B cell and antibody deficiencies have implications for treating autoantibody-related autoimmune diseases Studies have shown that CAR-T cells targeting B cell surface molecules can kill autoreactive B lymphocytes in pemphigus vulgaris PV and systemic lupus erythematosus SLE patients Thus CAR-T targeting antibody-producing cells has potential in treating autoimmune diseases including PV SLE autoimmune hemolytic anemia Sjogrens syndrome etc
MSCs have immune modulatory and immunosuppressive effects MSCs have been extensively studied and clinically evaluated for the treatment of autoimmune diseases and graft versus host disease GVHD caused by hematopoietic stem cell transplantation HSCT In many studies MSCs have demonstrated promising beneficial effects that can reduce severe autoimmune reactions In recent years MSCs have been used in synergy with CAR-T cells to address the shortcomings of CAR-T cells Fetal tissue-derived clonal MSCs fMSCs have extended expansion potential and express rich levels of various growth factors The fMSCs also resove a main limitation in MSC quality and reliability issues related to product consistency of MSCs As such innovative strategies to maximise the synergistic effects of CAR-Ts and MSCs have been proposed by either using MSCs as a supplementary intervention to assist in CAR-T based immunotherapies or as part of a sequential therapy regimen
CD19- and BCMA-specific CAR is based on activation of intracellular signalijng domains of T cells by the extracellular single chain variable fragment scFv antibodies against CD19 and BCMA The activated CAR-T cells can target and kill B cells The investigation plans to use genetically modified T cells to express 4th generation lentiviral CARs with an inducible caspase 9 self-withdrawal gene 4SCAR to increase the safety of this specific approach Besides targeting CD19 and BCMA other B cell and plasma cell surface molecules will also be targeted and included in the treatment design Based on accumulated experiences the 4SCAR T cells have shown high safety profile without serious cytokine release syndrome CRS or neural toxicities in patients Through this trial the safety and long-term efficacy of synergistic B-cell- and plasma-cell-specific 4SCAR T-cell therapy with MSCs will be evaluated providing clinical evidence to support the use of 4SCAR-T cells and MSCs in the treatment of autoimmune diseases
An ideal therapy to autoimmune disease should eradicate pathogenic autoimmune cells but retain the protective immunity The chimeric antigen receptor-modified T CAR-T cell technology has proven to be highly effective in targeting B cell malignancies and the treatment-induced B cell and antibody deficiencies have implications for treating autoantibody-related autoimmune diseases Studies have shown that CAR-T cells targeting B cell surface molecules can kill autoreactive B lymphocytes in pemphigus vulgaris PV and systemic lupus erythematosus SLE patients Thus CAR-T targeting antibody-producing cells has potential in treating autoimmune diseases including PV SLE autoimmune hemolytic anemia Sjogrens syndrome etc
MSCs have immune modulatory and immunosuppressive effects MSCs have been extensively studied and clinically evaluated for the treatment of autoimmune diseases and graft versus host disease GVHD caused by hematopoietic stem cell transplantation HSCT In many studies MSCs have demonstrated promising beneficial effects that can reduce severe autoimmune reactions In recent years MSCs have been used in synergy with CAR-T cells to address the shortcomings of CAR-T cells Fetal tissue-derived clonal MSCs fMSCs have extended expansion potential and express rich levels of various growth factors The fMSCs also resove a main limitation in MSC quality and reliability issues related to product consistency of MSCs As such innovative strategies to maximise the synergistic effects of CAR-Ts and MSCs have been proposed by either using MSCs as a supplementary intervention to assist in CAR-T based immunotherapies or as part of a sequential therapy regimen
CD19- and BCMA-specific CAR is based on activation of intracellular signalijng domains of T cells by the extracellular single chain variable fragment scFv antibodies against CD19 and BCMA The activated CAR-T cells can target and kill B cells The investigation plans to use genetically modified T cells to express 4th generation lentiviral CARs with an inducible caspase 9 self-withdrawal gene 4SCAR to increase the safety of this specific approach Besides targeting CD19 and BCMA other B cell and plasma cell surface molecules will also be targeted and included in the treatment design Based on accumulated experiences the 4SCAR T cells have shown high safety profile without serious cytokine release syndrome CRS or neural toxicities in patients Through this trial the safety and long-term efficacy of synergistic B-cell- and plasma-cell-specific 4SCAR T-cell therapy with MSCs will be evaluated providing clinical evidence to support the use of 4SCAR-T cells and MSCs in the treatment of autoimmune diseases
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None