NCT05631899

CAR-DC Vaccine and ICIs in Local Advanced/Metastatic Solid Tumors

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 Antibody/Anti-CTLA4 Antibody for Local Advanced/Metastatic Solid Tumors.

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot clinical trial for subjects with local advanced/metastatic 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 antibody/anti-CTLA4 antibody in patients with local advanced/metastatic solid tumors.

Conditions

• Solid Tumor, Adult
• EphA2 Overexpression
• KRAS G12V
• KRAS G12C
• KRAS G12D

Interventions

Type	Name	Description
BIOLOGICAL	KRAS-EphA-2-CAR-DC	5\~10 × 10\^6 CAR-DCs per dose will be administered by intravenous injection.
DRUG	Abraxane	Intravenous abraxane 125 mg/m\^2/day on day-5.
DRUG	Cyclophosphamide	Intravenous cyclophosphamide 300 mg/m\^2/day on day -4.
DRUG	Anti-PD-1 antibody	Intravenous anti-PD-1 antibody 200 mg/day.
DRUG	Anti-CTLA4 Monoclonal Antibody	Intravenous anti-CTLA4 antibody 1 mg/kg/day

Timeline

• Start date: 2023-04-03
• Primary completion: 2026-06-30
• Completion: 2026-12-30
• First posted: 2022-11-30
• Last updated: 2025-11-24

Locations

1 site across 1 country: China