In recent years, CAR-T therapy has made groundbreaking progress in hematologic malignancies and has started to expand into solid tumors. Meanwhile, TIL (tumor-infiltrating lymphocytes) and TCR-T (T cell receptor-engineered T cells) therapies hold great promise for advanced solid tumors. NK (natural killer) cells and CAR-NK cell therapies have also become research focuses due to their innate immune functions and safety advantages. The continued advancement and breakthroughs in immunotherapy have not only brought new choices and hope to cancer patients but also ushered in a new era in cancer treatment. In this article, Dr. Qin Haifeng, Director of the Thoracic Oncology Department at Beijing GoBroad Hospital, and Dr. Qin Lili, systematically explain the categories of immunotherapy and recent progress in each type.

 

Progress in Clinical Research of TILs for Advanced Solid Tumors

 

Tumor-infiltrating lymphocytes (TILs) are a population of T cells with natural anti-tumor activity found within tumor tissues. These cells have two important characteristics:

1. The ability to survive in a complex tumor microenvironment.
2. The innate ability to recognize and kill tumor cells.

Research has shown that TILs have a high tropism for tumors, which allows them to actively target and gather in tumor regions, making them key effector cells in tumor immunotherapy.

The core process of TIL therapy includes:

• Obtaining tumor samples from patients.
• Isolating and expanding TILs in the lab to a therapeutic dose.
• Re-infusing them into the patient.
• Administering immune factors such as interleukin-2 (IL-2) to promote further expansion and targeted tumor killing in the body.

TILs are derived directly from the tumor and exhibit greater tumor specificity. Despite the complex and time-consuming preparation process, their therapeutic potential in solid tumor patients is gradually becoming evident.

 

FDA Approves First TIL Product Showing Efficacy in Melanoma

In 2024, the U.S. FDA approved the world’s first TIL product, LN-144 (developed by Iovance Biotherapeutics), for second-line treatment of advanced melanoma. LN-144 is currently the only approved TIL therapy for solid tumors and has shown over 30% objective response rate (ORR) in multiple international studies—significantly outperforming targeted drugs and immune checkpoint inhibitors, which typically yield ORRs of 10–20%.

This approval was based on the C-202 trial by Iovance, which involved multiple solid tumor types including melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma. The trial validated the therapeutic potential of standardized TIL extraction and infusion protocols for recurrent or refractory solid tumors.

 

Initial Success of Domestic TIL Projects

Many Chinese biotech firms and research centers are actively developing TIL-related therapies. The GT101 project, involving Dr. Qin Haifeng’s team, has completed Phase I trials in cervical cancer and other solid tumors, achieving an ORR of 45.4%, a notable result. These findings were presented as a poster at the 2024 ASCO Annual Meeting.

Dr. Qin’s team is now conducting upgraded TIL protocols across various cancer types and treatment stages. Some patients have even achieved complete pathological remission (pCR), showing strong clinical potential.

 

Clinical Progress in NK Cell Therapy

 

Natural Killer (NK) cells are key components of the innate immune system with the ability to recognize and eliminate tumors without antigen presentation. Due to their safety profile and treatment potential, they have garnered increasing attention in cancer immunotherapy.

NK cell therapy is already being applied in hematologic malignancies (e.g., lymphoma, leukemia) and is being actively explored in solid tumors such as:

• Liver cancer
• Breast cancer
• Small cell lung cancer
• Nasopharyngeal carcinoma
• Ovarian cancer

However, broad application faces technical challenges:

• Therapeutic efficacy depends heavily on NK cell activity and quantity.
• Factors such as a patient’s physical condition, immune status, and collection quality affect outcomes.
• Some patients’ NK cell activity is insufficient for effective treatment.

Thus, developing "universal" NK cell products—derived from healthy donors, standardized for mass production, and ready for use—has become a major research focus.

 

Clinical Case Highlights

1. A 52-year-old female with endometrial cancer showed significant shrinkage of lymph node metastases and reduced tumor burden after receiving universal NK cell infusion.
2. A 72-year-old male lung cancer patient with multiple lymph node metastases received NK cells combined with PD-1 inhibitor therapy. Although tumor shrinkage couldn't be directly measured due to imaging limitations, his quality of life improved significantly post-treatment without serious adverse reactions, underscoring the therapy's clinical promise.

 

Progress in CAR-NK Cell Therapy

 

CAR-NK therapy integrates CAR technology with NK cells, combining specific antigen recognition with NK cells' inherent safety and low toxicity. It represents a significant development in cell therapy.

Current CAR-NK research targets several solid tumor antigens:

• B7-H3
• Claudin 18.2
• HER-2
• TROP2

Clinical Advantages

CAR-NK therapy has demonstrated:

• Excellent safety profile
• Lower or controllable incidence of immune-related side effects such as:
• Cytokine release syndrome (CRS)
• Neurotoxicity (ICANS)
• Graft-versus-host disease (GVHD)

These advantages are due to:

• NK cells’ short in vivo lifespan and limited expansion.
• No autologous infusion required, simplifying preparation and lowering costs.
• Greater accessibility for a wider patient population.

 

Advances in Tumor Vaccine Therapy

 

Tumor vaccines aim to activate the body’s adaptive immune system by inducing or enhancing T cell recognition and attack on tumor-specific antigens to control or prevent cancer progression.

Types of tumor vaccines include:

• DNA vaccines
• RNA vaccines
• Peptide vaccines
• Dendritic cell (DC) vaccines

These have been studied in melanoma, lung cancer, ovarian cancer, and more. Some have reached Phase II/III trials, especially when combined with immune checkpoint inhibitors (e.g., PD-1/PD-L1 antibodies), showing synergistic effects and improving patient outcomes.

 

Domestic Breakthroughs in Tumor Vaccine R&D

China has also seen advances in original vaccine development. The first FDA-approved domestic mRNA tumor vaccine, LK101, integrates mRNA technology with dendritic cell delivery, and targets post-operative recurrence risk in liver cancer.

Initial studies show LK101 significantly:

• Prolonged 2-year recurrence-free survival (RFS)
• Improved overall survival (OS)

This suggests broad prospects for adjuvant immunotherapy after curative treatments.

 

Conclusion

Tumor cellular immunotherapy is rapidly evolving from research to clinical application, bringing real survival benefits to patients with advanced or refractory cancers. As immunotherapies continue to mature, we are entering a new stage of precise and durable tumor control.