Lesion Reduced by 71.3%! Inybrain NK Cell Therapy Breaks Through Bottlenecks in Liver Cancer Treatment
- Elva Chen
- 2 days ago
- 6 min read
According to the latest report published in The Lancet in July 2025, there are 870,000 new liver cancer cases and 760,000 deaths worldwide each year, with nearly half of these new cases and deaths occurring in China.
According to the 2022 China Cancer Statistics released by the National Cancer Center in 2024, there are 367,700 new liver cancer cases and 316,500 deaths in China each year.
Liver cancer has become a "silent killer" threatening human health. Although traditional treatments such as surgery, chemotherapy, targeted therapy and immunotherapy have contributed greatly to liver cancer treatment, they still struggle to break through bottlenecks including tumor microenvironment suppression, treatment-related adverse reactions and poor efficacy in advanced stages.
In recent years, the rise of NK (Natural Killer) cell therapy has brought new hope for liver cancer treatment. It has shown impressive therapeutic potential from basic research to clinical cases, becoming an important breakthrough to solve the dilemma of liver cancer treatment.
Current Status of Liver Cancer Treatment:
The Dilemma of Traditional Therapy Amid High Incidence
Clinically, liver cancer is mainly divided into hepatocellular carcinoma (HCC, accounting for 75%–85%) and intrahepatic cholangiocarcinoma (iCCA, accounting for 10%–15%). The 2024 edition of Guidelines for the Diagnosis and Treatment of Primary Liver Cancer defines standard treatment regimens for different stages: surgery is the core for early-stage disease; transarterial chemoembolization (TACE) combined with targeted/immunotherapy is the main approach for intermediate and advanced stages; and systemic therapy with PD-1/PD-L1 inhibitors plus anti-angiogenic agents is the first choice for terminal stages. Despite standardized treatment protocols, traditional treatments still have many limitations.
Limitations of Conventional Treatments
NK Cells in the Body:
Why Are "Natural Immune Warriors" Impeded?
The shortcomings of traditional treatments have made it difficult to significantly improve the survival of patients with intermediate and advanced liver cancer, prompting researchers to focus on more promising cellular immunotherapy — NK cell therapy.
NK cells are the "rapid response force" of the body’s innate immune system. They can directly recognize and kill cancerous cells without prior sensitization, precisely eliminating tumor cells by releasing perforin and granzyme to break down tumor cell membranes, making them "natural immune warriors" against cancer.
Theoretically, endogenous NK cells should serve as the main force against liver cancer. However, in patients with liver cancer, NK cell function is severely suppressed due to two core issues:
1.Inhibitory effects of the tumor microenvironment on NK cells
(1) Metabolic reprogramming: Liver cancer cells cause metabolic disorders such as glycolysis, leading to lactic acid accumulation and amino acid depletion in the microenvironment, directly inhibiting NK cell proliferation and cytotoxicity.
(2) Angiogenesis and stromal barrier: Tumor-associated angiogenesis and physical barriers formed by fibroblasts block NK cell infiltration into the tumor core.
(3) Immune cell polarization: Macrophages are polarized to immunosuppressive M2 phenotype and secrete cytokines such as IL-10 and TGF-β; fibroblasts also secrete inhibitory factors, collectively impairing endogenous NK cell function.
2.NK cell exhaustion mediated by immune checkpoint pathways
Liver cancer cells inactivate NK cells and induce exhaustion by activating inhibitory receptor-ligand pairs:
(1) Key inhibitory receptor-ligand pairs:
· PD-1/PD-L1: High expression of PD-L1 on liver cancer cells binds to PD-1 on NK cells, inhibiting the secretion of granzyme and perforin.
· Tim-3/Galectin-9/Ceacam-1: Tim-3 binding to its ligand blocks NK cell activation signals and reduces the production of cytokines such as IFN-γ.
· LAG-3/FGL1: LAG-3 binds to FGL1 secreted by liver cancer cells, inhibiting NK cell proliferation and cytotoxicity.
· TIGIT/CD155: TIGIT binding to CD155 weakens signals from activating receptors (e.g., NKG2D) on NK cells and induces functional exhaustion.
(2) Impaired effector molecules: In the exhausted state, NK cells show significantly reduced secretion of perforin and granzyme, greatly diminishing their ability to directly kill liver cancer cells.
The Way Out:
Therapeutic Strategies of NK Cell Therapy
To address the core issue of impaired NK cell function in liver cancer patients, researchers have developed a series of targeted strategies. Through ex vivo modification and functional activation, "armed" NK cells gain enhanced killing capacity, break through the tumor microenvironment barrier after infusion, and become "super soldiers" against liver cancer. There are two mainstream strategies:
Strategy 1: Equip NK cells with "precision navigation"
Using gene editing (the technology adopted by most companies) or antibody-cell conjugation (Inybrain’s core technology), antigen receptors are introduced into NK cells, like equipping them with precision navigation. This enables NK cells to specifically recognize liver cancer-associated antigens, bypass immunosuppressive signals in the tumor microenvironment, and exert direct killing effects.
Strategy 2: Revitalize NK cells to full capacity
Restore NK cell killing function through cytokine activation, activating receptor stimulation and inhibitory pathway blockade.
· Cytokine priming: Cytokines such as IL-12, IL-15 and IL-18 bind to NK cell surface receptors, enhancing proliferation, cytokine secretion and killing capacity.
· Activation of ADCC effect: CD16 on NK cells binds to the Fc segment of liver cancer-targeting antibodies, mediating antibody-dependent cellular cytotoxicity for specific killing.
· Inhibitory pathway blockade: Anti-PD-1/Tim-3 antibodies and TGF-β inhibitors release suppressive signals and reactivate exhausted NK cells.
Clinical Evidence:
Impressive Results of NK Cell Therapy
In June 2022, a study led by Chonnam National University Medical School and Chonnam National University Hwasun Hospital on the efficacy and safety of chemotherapy combined with NK cell therapy in patients with advanced liver cancer refractory to standard treatment was published in Frontiers in Immunology.
The study showed that 11 patients with advanced liver cancer refractory to standard treatment received 4 cycles of transarterial infusion chemotherapy (5-fluorouracil + cisplatin), followed by 5 consecutive days of dose-escalated infusions of expanded and activated NK cells. The combination therapy demonstrated good safety with no severe adverse events; the objective response rate was 63.6%, disease control rate 81.8%, and median overall survival 41.6 months; tumor markers were significantly reduced. This confirmed that the combination therapy is safe and effective for these patients, far exceeding expectations of traditional advanced liver cancer treatment.
Another study published in 2021 verified that NK cell therapy is safe and significantly effective in preventing long-term recurrence after liver cancer surgery. Researchers administered 5 cycles of NK cell therapy at weeks 4, 6, 8, 12 and 16 postoperatively to 5 patients with hepatocellular carcinoma who underwent hepatectomy.
The results showed that NK cell therapy was well tolerated with no drug-related adverse events. After a median follow-up of 43 months, the 3-year recurrence-free survival rate was 60% and overall survival rate 80%. The proportion of CD8+ T lymphocytes in recurrence-free patients was significantly higher than in those with recurrence, suggesting that NK cell therapy may prevent long-term recurrence of liver cancer.
Inybrain Cases:
Breaking Through Liver Cancer Treatment Bottlenecks
Case 1: Lesion reduced by 71.3%, tumor markers decreased, HBV viral load dropped to normal
Patient with primary liver cancer and chronic hepatitis B virus infection. Multiple space-occupying lesions in the left liver, maximum diameter 28 mm; tumor thrombus in the main trunk and bilateral branches of the portal vein (the main blood supply vessel of the liver) — a pathological condition where malignant tumor cells invade the portal venous system and form cancerous emboli, causing partial or complete obstruction, commonly seen in advanced liver cancer and severely impairing liver function. Tumor markers AFP and CA125 were abnormally elevated.
After two Inybrain tiNK therapy interventions with a 2-month interval, hepatitis B virus DNA load decreased to normal; tumor markers dropped significantly; imaging showed the nodular abnormal lesion in the left hepatic lobe (original 28 mm) shrank to 15 mm, and portal vein branch tumor thrombus exhibited regression.
Case 2: Four years of no recurrence or metastasis, long-term stability after surgery for high-risk double primary cancer
Patient with double primary cancer, diagnosed with cholangiocarcinoma and lung cancer successively within more than 1 year. The patient could not tolerate chemotherapy due to adverse reactions. For nearly 4 years after surgery, the patient has relied solely on Inybrain ACC-NK interventions. Regular follow-ups showed no signs of recurrence or metastasis. The condition changed from high metabolic tumor status shown by preoperative PET-CT to long-term tumor-free status, with encouraging efficacy.
Future Outlook:
NK Cell Therapy Ushering in a New Era of Combination Therapy for Liver Cancer
Current research and clinical data demonstrate that NK cell therapy, with its advantages of high specificity, high safety and no obvious adverse reactions, has become a new direction for liver cancer treatment. It shows irreplaceable value especially in the treatment of intermediate and advanced liver cancer and liver cancer with high postoperative recurrence risk.
The core trend of liver cancer treatment in the future will undoubtedly be combination therapy: the combined application of NK cell therapy with traditional treatments and even more cutting-edge technologies. Through multi-modal synergy, this approach will break immunosuppression in the tumor microenvironment, activate the body’s comprehensive anti-tumor immunity, and enable more liver cancer patients to achieve long-term survival and even clinical cure. Fighting liver cancer is a protracted battle, and medical advances are bringing us closer to victory.
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