NCT05631886

Combination of CAR-DC Vaccine and ICIs in Malignant Tumors

A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With TP53 Mutant Peptide Plus ICIs for Local Advanced/Metastatic Solid Tumors or Relapsed/Refractory Lymphomas.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• 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 or relapsed/refractory (R/R) lymphomas to determine the safety, efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with TP53 mutant peptide (TP53-EphA-2-CAR-DC) in combination with ICIs. It aims to: assess the safety and antitumor effects of TP53-EphA-2-CAR-DC vaccine; detect T cell response against TP53 mutant peptide and tumor neoepitopes after the treatment with TP53-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 malignant tumors. Therefore, we designed an autologous CAR-DC vaccine engineered with anti-EphA2 CAR and TP53 mutant peptide (TP53-EphA-2-CAR-DC), which can suppress the growth of tumors expressing the correlated TP53 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 TP53-EphA-2-CAR-DC combined with anti-PD-1 antibody/anti-CTLA4 antibody in patients with local advanced/metastatic solid tumors or R/R lymphomas.

Conditions

• Solid Tumor, Adult
• Lymphoma
• EphA2 Overexpression
• TP53 R273H
• TP53 R175H
• TP53 R248Q
• TP53 R249S

Interventions

Type	Name	Description
BIOLOGICAL	TP53-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: 2023-07-04
• Primary completion: 2025-12-30
• Completion: 2026-12-30
• First posted: 2022-11-30
• Last updated: 2023-08-28

Locations

1 site across 1 country: China