Malignant solid tumors are a group of cancers that form solid masses in organs or tissues, originating from the lung, liver, pancreas, breast, colon, and other organs. These tumors are often characterized by rapid growth, invasion into surrounding tissues, and the potential to metastasize to distant organs.

The treatment of malignant solid tumors is challenging due to tumor heterogeneity, which means that cancer cells within the same tumor can vary in their molecular and genetic profiles, leading to treatment resistance. Conventional therapies such as surgery, chemotherapy, radiotherapy, and targeted drugs often have limited efficacy in advanced or metastatic cases. Additionally, the tumor microenvironment can suppress the immune system, further reducing treatment success.

The fourth-Generation CAR-T cells facilitate the recruitment of endogenous T cells and dendritic cells to the tumor site, addressing the limitations of conventional CAR-T in immunosuppressive environments. The fourth-Generation CAR-T cells are designed to target both Nectin4 and fibroblast activation protein (FAP), thereby addressing both tumor cell heterogeneity and tumor microenvironment. The dual-target strategy aims to reduce antigen escape, enhance antitumor efficacy, and potentially decrease recurrence rates.

This clinical trial is currently recruiting patients worldwide, providing an investigational treatment option for patients with refractory, unresectable, or unsuitable malignant solid tumors for standard local treatment.

Treatment Protocol

Intervention Overview

Patients with Nectin4-positive advanced malignant solid tumors receive a minimally invasive intravenous and intratumoral administration of fourth-generation CAR-T cells targeting Nectin4 and FAP. These engineered CAR-T cells, expressing IL-7 and CCL19 or IL-12, are designed to eliminate residual tumor cells, modulate the tumor microenvironment, and reduce the risk of recurrence.

• Enhancing T Cell Proliferation and Persistence: IL-7 supports the survival and expansion of CAR-T cells after infusion, ensuring that the therapy remains active in the patient for a longer period.
• Recruitment of Immune Cells: CCL19 is a chemokine that attracts additional immune cells, such as dendritic cells and T cells, to the tumor site.
• Direct Anti-Tumor Immunomodulation: IL-12 stimulates T cells and natural killer (NK) cells, boosting their cytotoxic activity against tumor cells.
• Reduced Risk of Tumor Escape and Recurrence: By combining enhanced T cell activity, immune cell recruitment, and microenvironment modulation, these CAR-T cells are better equipped to eradicate residual cancer cells and prevent tumor relapse.

Fourth-Generation Dual CAR-T Cells Targeting Nectin-4 and FAP

Treatment Process

• Screening and Enrollment: Comprehensive medical evaluation, including tumor assessment, organ function tests, and eligibility confirmation based on inclusion/exclusion criteria.
• T-Cell Collection: Peripheral blood mononuclear cells are collected from the patient to isolate T cells.
• CAR-T Cell Engineering: T cells are genetically modified ex vivo to express the Nectin4/FAP CAR, expanded to therapeutic quantities, and undergo rigorous quality control.
• CAR-T Cell Infusion: Engineered CAR-T cells are infused intravenously, with dosing schedules determined by safety and trial protocol.
• Monitoring and Follow-Up: Patients are closely monitored for treatment-related toxicities and therapeutic response. Imaging and laboratory tests are performed at defined intervals to evaluate tumor response and CAR-T cell persistence.

Patient Recruitment Criteria

Treatment Cost

This clinical study is a chargeable treatment program. Participating patients are responsible for the costs of the study intervention and related examinations. The costs mainly include:

• Cost of CAR-T cell preparation and injection treatment;
• Cost of necessary blood, imaging, and other laboratory tests during treatment;
• Fees for basic medical services during hospitalization (such as nursing care, medication, etc.).

For detailed fees, travel/visa support, accommodation and logistics, please contact us for a personalized consultation.

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