Ignite Creation Date:
2024-05-06 @ 6:22 PM
Last Modification Date:
2024-10-26 @ 2:46 PM
Study NCT ID:
NCT05631899
Status:
RECRUITING
Last Update Posted:
2024-02-06
First Post:
2022-11-21
Brief Title:
CAR-DC Vaccine and ICIs in Local AdvancedMetastatic Solid Tumors
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With KRAS Mutant Peptide in Combination With Anti-PD-1 AntibodyAnti-CTLA4 Antibody for Local AdvancedMetastatic Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-02
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:
This is a pilot clinical trial for subjects with local advancedmetastatic solid tumors to determine the safety efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with KRAS mutant peptide KRAS-EphA-2-CAR-DC in combination with ICIs It aims to assess the safety and antitumor effects of KRAS-EphA-2-CAR-DC vaccine detect T cell response against KRAS mutant peptide and tumor neoepitopes after the treatment with KRAS-EphA-2-CAR-DC vaccine and ICIs
Detailed Description:
Therapeutic cancer vaccines especially DC-based vaccines are extensively pursued immune approaches in addition to immune checkpoint blockade antibodies and chimeric antigen receptor T cells DCs can engulf process and present tumor antigens to T cells thereby initiating a potent and tumor-specific immune response However clinical outcomes of therapeutic cancer vaccines still remain poor with objective response rates that rarely exceed 15 The maturation and activation of DCs are necessary steps to trigger the antitumor responses However it is increasingly clear that tumor-infiltrating dendritic cells TIDCs usually have an immature or tolerated phenotype that plays central roles in developing tumor microenvironment TME As a consequence malfunction of TIDCs could suppress the infiltration and function of tumor infiltrating T cells and convert them into immune suppressive regulatory T cells
In our previous research we constructed novel CAR-DCs Chimeric antigen receptor engineered dendritic cells containing a scFv domain targeting EphA2 antigen CD8a transmembrane tandem DC-specific activation domains The engineered CAR-DCs were activated when contacting with tumor targets in TME and consequently augmented the cytotoxicity of antigen specific T cells in immune system humanized solid tumor mouse models Our design of CAR-DCs provides an effective vaccine strategy for solid tumors Therefore we designed an autologous CAR-DC vaccine engineered with anti-EphA2 CAR and KRAS mutant peptide KRAS-EphA-2-CAR-DC which can suppress the growth of tumors expressing the correlated KRAS mutant in animal models In addition the combination of the immune checkpoint inhibitors could further reverse immunosuppressive TME and globally activate T cell responses In this pilot study we aim to assess the safety efficacy and immune response of KRAS-EphA-2-CAR-DC combined with anti-PD-1 antibodyanti-CTLA4 antibody in patients with local advancedmetastatic solid tumors
In our previous research we constructed novel CAR-DCs Chimeric antigen receptor engineered dendritic cells containing a scFv domain targeting EphA2 antigen CD8a transmembrane tandem DC-specific activation domains The engineered CAR-DCs were activated when contacting with tumor targets in TME and consequently augmented the cytotoxicity of antigen specific T cells in immune system humanized solid tumor mouse models Our design of CAR-DCs provides an effective vaccine strategy for solid tumors Therefore we designed an autologous CAR-DC vaccine engineered with anti-EphA2 CAR and KRAS mutant peptide KRAS-EphA-2-CAR-DC which can suppress the growth of tumors expressing the correlated KRAS mutant in animal models In addition the combination of the immune checkpoint inhibitors could further reverse immunosuppressive TME and globally activate T cell responses In this pilot study we aim to assess the safety efficacy and immune response of KRAS-EphA-2-CAR-DC combined with anti-PD-1 antibodyanti-CTLA4 antibody in patients with local advancedmetastatic solid tumors
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