PD-1/PD-L1 inhibitors and CAR-T therapies can mostly only recognize targets on the cell surface—they are nearly powerless against tumor antigens hidden inside cells. One of the primary "stealth agents" in solid tumors is a molecule known asPRAMEOncoprotein.

PRAME is nearly silent in normal adult tissues but becomes highly “awakened” in various solid tumors, including ovarian cancer, lung squamous cell carcinoma, triple-negative breast cancer, melanoma, and esophageal cancer. Studies have shown that over 80% of ovarian cancer patients exhibit high PRAME expression. Its aberrant activity is one of the drivers behind the rampant proliferation of tumors.

Now, the "hiding in cells" target has finally been targeted.

In April 2025, the top-tier medical journal **Nature Medicine** published the most significant Phase 1 clinical data to date for PRAME-targeted TCR-T therapy (NCT03686124).

In 40 patients with advanced solid tumors who had failed multiple lines of therapy, after a single infusion:

• Objective Response Rate (ORR) as high as52.5%, more than half of the patients showed measurable tumor shrinkage
• The median progression-free survival (mPFS) in the high-dose group reached5.7months, superior to historical control data
• Median overall survival (mOS) in the 1b high-dose group has not been reached, with the survival curve still extending.
• TCR-T cells can persist in peripheral blood for over 2 years, establishing durable immune memory
• The most severe adverse reactions were reversible low-grade CRS (grades 1–2), with no grade 4/5 serious events.Overall Safety and Controllability

This represents one of the most compelling clinical evidences to date for TCR-T cell therapy in the treatment of solid tumors.

T cell receptor-engineered T cell (TCR-T) therapy has a key difference from CAR-T:

CAR-T can only recognize proteins exposed on the cell surface; whereasTCR-T cells can penetrate the cell surface and recognize intracellular antigens that are "presented on the cell surface" by MHC-I molecules.。

This means that as long as tumor cells are "alive" and translating the PRAME protein, they have nowhere to hide—even if this antigen is deeply concealed within the cell.

Independently developed by Neowise Biotechnology (Suzhou) Co., Ltd.NW-101, an autologous TCR-T cell therapy specifically designed to target PRAME, is currently conducting Phase I clinical trials at multiple cancer centers across China, with simultaneous recruitment for various solid tumor types.

Inclusion Criteria (Partial)

Applicable Cancer Types (Applications Accepted After First-Line Treatment Failure):

✅ Ovarian Cancer (Platinum-Resistant, Post-First-Line)
✅ Squamous Cell Lung Cancer (Post-First-Line)
✅ Triple-Negative Breast Cancer (Post-First-Line)
✅ Synovial Sarcoma (Post-First-Line)
✅ Melanoma (Post-First-Line)
✅ Esophageal Cancer (Post-Second-Line)

Core Inclusion Criteria:

1. Age 18-75 years, ECOG performance status score 0-1
2. HLA Typing: Must include the HLA-A*02:01 subtype (confirmed via blood test)
3. PRAME Expression: Positive for PRAME by IHC testing of tumor pathological tissue (either fresh or FFPE blocks are acceptable)
4. Prior failure, recurrence, or intolerance to standard therapy
5. Presence of at least one measurable lesion (RECIST 1.1)

Clinical Benefit for Patients

1）Free Medication: The investigational drug is provided free of charge until disease progression.

2）Free Examination: After obtaining informed consent, all study-related examinations will be provided free of charge.

3）Transportation Allowance: Transportation allowance related to clinical research.

4）Regular Follow-up by Specialists: Comprehensive expert team services, with the institution maintaining long-term monitoring of patients' health conditions.

Project Implementation Region

This study is currently being conducted across multiple centers nationwide in China; specific details are subject to confirmation through subsequent consultation.

Summary of Materials to Be Submitted

Materials to be prepared and submitted by the patient include:Pathology Report, Genetic Testing Report, Admission Record, Discharge Summary, CT/MRI Examination, Complete Blood Count (CBC), Liver and Kidney Function Tests, Coagulation Profile, Infectious Disease Screening, Electrocardiogram (ECG) Reportetc.

Global Oncology Division: Friendly Reminder

If you wish to participate in this clinical study or obtain more information, please submit your medical records toGlobal Oncologist Network Medical Department (400-666-7998), obtain more information on domestic and international applications, or apply directly. We commit to maintaining the confidentiality of all participants' personal information and guarantee compliance with national laws and regulations related to clinical research throughout the process.

Cellular Immunity