Conditions

Advanced Breast Cancer Breast Neoplasm Malignant Female

Keywords

Breast cancer, solid tumor, CAR-T cells, PD-1 knockout, MUC1

Outcome Measures

Primary Outcomes (3)

Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v5.0
3 years
Incidence of treatment-emergent adverse events [safety and tolerability] of dose of PD-1 Knockout CAR-T cells will be assessed using CTCAE v5.0
3 years
Monitoring the numbers of circulating AJMUC1 after infusion will be evaluated.
up to 3 years

Secondary Outcomes (4)

Response rate will be assessed according to the revised RECIST guideline iRECIST
3 years
Overall Survival - OS (Measure the time from enrollment to death)
3 years
Progression free survival - PFS (Time from enrollment to date of first documented progression or date of death)
3 years
Median CAR-T cell persistence--Will be measured by quantitative RT-PCR
3 years

Other Outcomes (1)

To evaluate serum cytokine changes after AJMUC1 treatment of aberrantly glycosylated MUC1 expression in advanced breast cancer
3 years

Study Arms (1)

Treatment with AJMUC1--PD-1 knockout CAR-T cells

EXPERIMENTAL

Advanced breast cancer patients with positive MUC1 expression are the indications of this clinical study. Current conventional treatments are ineffective for these patients or there is no effective treatment plan available for them. No control group is established and a single arm design is used. This clinical study is the first application of AJMUC1 in the clinical treatment of MUC1-positive advanced breast cancer patients. The main purpose is to assess the safety and feasibility of the product in clinical use. Therefore, according to the principle of "3+3" dose escalation design, this study explored the maximum tolerated dose of AJMUC1 for the treatment of MUC1-positive advanced breast cancer. At the same time, the efficacy of AJMUC1 in the treatment of MUC1-positive advanced breast cancer will be observed and factors that could affect the safety and efficacy of the therapy will be exploringly evaluated.

Drug: AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cells

Interventions

AJMUC1- PD-1 gene knockout anti-MUC1 CAR-T cellsDrug

AJMUC1 is a genetically modified T cell therapeutic product targeting the aberrantly glycosylated MUC1 protein. CAR targeting MUC1 is introduced into autologous T cells by lentiviral vector, so that T cells expressing the receptor can recognize and kill MUC1 positive tumor cells. Preclinical studies have shown that binding of scFv targeting MUC1 to the MUC1 epitope on the surface of the target cell can induce the costimulatory CD28 and CD3ζ costimulatory domains to activate downstream signaling pathways and promote T cell activation and expansion. Activated CAR-T cells secrete a series of inflammatory cytokines and chemokines, leading to apoptosis and necrosis of target tumor cells. Following introduction of a CAR structure, the PD-1 gene of CAR-T cells is knocked out using CRISPR/Cas9, so that the CAR-T cell does not express PD-1, resulting in improved tumor killing efficiency of AJMUC due to the release of inhibition in the signaling pathway PD-1/PD-L1 in the tumor microenvironment.

Also known as: Therapeutic T cells

Treatment with AJMUC1--PD-1 knockout CAR-T cells

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age18 Years - 70 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patient age: 18-70 years (including the boundary value);
Pathologically diagnosed with recurrent/metastatic breast cancer (except for intracranial metastasis), who have received at least one standard treatment regimen in the past, the disease is in a stable or progressive state, and refuses to undergo subsequent chemotherapy;

Sponsors & Collaborators

Guangzhou Anjie Biomedical Technology Co., Ltd.
Industrycollaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Otherlead

Study Sites (1)

Sun Yat-sen Memorial Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

Erwei Song, MD, PhD
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
PRINCIPAL INVESTIGATOR

PD-1 Knockout Anti-MUC1 CAR-T Cells in the Treatment of Advanced Breast Cancer

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

Study Start

First Submitted

Primary Completion

Study Completion

First Posted

Conditions

Keywords

Outcome Measures

Primary Outcomes (3)

Secondary Outcomes (4)

Other Outcomes (1)

Study Arms (1)

Treatment with AJMUC1--PD-1 knockout CAR-T cells

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Links

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Locations

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

Primary Completion

Study Completion

First Posted

Conditions

Keywords

Outcome Measures

Primary Outcomes (3)

Secondary Outcomes (4)

Other Outcomes (1)

Study Arms (1)

Treatment with AJMUC1--PD-1 knockout CAR-T cells

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Links

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Locations