PD-1/PD-L1 inhibitors and CAR-T can mostly only recognize targets on the cell surface – they are nearly powerless against tumor antigens hidden inside cells. One of the main "hide-and-seek players" in solid tumors is a type calledPRAMEThe oncogene protein.

PRAME is almost silent in normal adult tissues but highly "awakened" in various solid tumors such as ovarian cancer, squamous cell carcinoma of the lung, triple-negative breast cancer, melanoma, and esophageal cancer—studies have shown that the proportion of PRAME high expression in ovarian cancer patients exceeds 80%. Its abnormal activity is one of the drivers behind the rampant proliferation of tumors.

Now, this "hidden-in-cell" target has finally been targeted.

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

Among 40 patients with advanced solid tumors who failed multiple lines of treatment, after a single infusion:

• Objective Response Rate (ORR) as high as52.5%, more than half of the patients' tumors showed measurable shrinkage.
• The median progression-free survival (mPFS) in the high-dose group reached5.7Months, better than the historical control data
• Median overall survival (mOS) in the 1b high-dose group has not yet been reached, and the survival curve is still extending.
• TCR-T cells can persist in peripheral blood for more than 2 years, creating lasting immune memory.
• The most severe adverse reaction was reversible low-grade CRS (Grade 1-2), with no Grade 4/5 serious events.Overall safety is controllable

This is one of the most compelling clinical pieces of evidence for TCR-T cell therapy against solid tumors to date.

T Cell Receptor-Engineered T Cells (TCR-T) Therapy Has a Key Difference from CAR-T:

CAR-T can only recognize proteins exposed on the cell surface; whereasTCR-T can penetrate the cell surface and recognize intracellular antigens 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 hidden inside the cell.

Neowise Biotechnology, Co., Ltd. (Suzhou) independently developedNW-101It is an autologous TCR-T cell therapy specifically designed for the PRAME target, and its Phase I clinical trial is currently being conducted at multiple cancer centers across China, with synchronous recruitment for various types of solid tumors.

Inclusion Criteria (Partial)

Applicable Cancer Types (All can be applied after the failure of first-line treatment):

✅ Ovarian Cancer (Platinum-Resistant, Post-Frontline)
✅ Squamous Cell Carcinoma of the Lung (Post First-Line)
✅ Triple-Negative Breast Cancer (Post First-Line)
✅ Synovial Sarcoma (Post First-Line)
✅ Melanoma (Post First-Line)
✅ Esophageal Cancer (Second-Line and Beyond)

Core Enrollment Criteria:

1. Aged 18-75 years, ECOG performance status score 0-1
2. HLA Typing: Must contain the HLA-A*02:01 subtype (can be confirmed through a blood test)
3. PRAME Expression: IHC Detection of PRAME Positivity in Tumor Pathological Tissues (Fresh or FFPE Blocks Acceptable)
4. Previous standard treatments have failed, recurred, or were not tolerated.
5. At least one measurable lesion (RECIST 1.1)

Clinical Benefit to Patients

1）Free Medication: The study drug will be provided free of charge until disease progression.

2）Free Examination: Related examinations required for the trial will be free of charge after being informed.

3）Transportation Allowance: Traffic subsidies related to clinical research.

4）Regular Follow-up by Experts: Full-service expert team, the institution pays long-term attention to the patient's physical condition.

Project Implementation Region

This study is currently being conducted in multiple centers across China, and specific details will be confirmed through later inquiries.

Summary of Required Documents

The materials that patients need to prepare and submit include:Pathology Report, Genetic Testing Report, Admission Record, Discharge Summary, CT/MRI Examination, Complete Blood Count, Liver and Kidney Function, Coagulation Function, Infectious Disease Screening, Electrocardiogram Reportetc.

Global Oncology Department Kindly Reminder

If you would like to participate in this clinical study or learn more information, you can submit your medical records toGlobal Cancer Doctors Network Medical Department (400-666-7998), obtain more information about applications both in China and internationally, or apply directly. We commit to keeping all participants' personal information confidential and guarantee adherence to national laws and regulations related to clinical research throughout the process.

Cellular Immunity