With the development of medicine, although cancer treatment methods are emerging one after another, cancer cure is still out of reach, and the emergence of immune cell therapy has made it possible to cure cancer.
immune cells has made breakthrough progress in tumor treatment, and currently NK cell therapy is the most promising seed player;
NK cells play an important role in tumor immune and have achieved significant results in the treatment of a variety of malignant tumors, including lung cancer, gastric cancer , liver cancer , breast cancer , ovarian cancer and some blood tumors.
months: The metastatic lesions completely disappeared
A 51-year-old woman developed lower abdomen pain, swelling, and a sense of compression in her chest in December 2008. She was diagnosed with pancreatic cancer , and metastasis in many parts of the lungs, liver and other parts.
Since it is not suitable for surgery and radiotherapy, chemotherapy can only be used. In January 2009, the CA19-9 value rose to 318417.
Highly activated NK cell therapy began in February 2009. After the first NK cell treatment, the CA19-9 value dropped to 7355 on February 12, 2009. After the fourth NK cell treatment, the CA19-9 value dropped to 141, and the CEA and CA125 values also improved.
CT examination in May 2009, and the results of indicate that the tumor metastasized to the liver and lung trachea lymph node disappeared, and the primary pancreatic tumor also began to disappear.
Surprise: The tumor basically disappeared
A 74-year-old male patient was diagnosed with stage 4 colon cancer in May 2008 and underwent surgery. In June, he found that he had metastasized to 25 livers.
html Chemotherapy began in 16 months and highly activated NK cell therapy began in July. The results of the examination after 7 chemotherapy and 5 NK cell therapy showed that the boundary of
metastasized to the largest tumor in the liver began to blur, and there were signs of shrinking. In addition, the two tumors with obvious shapes have disappeared.
chemotherapy 12 times, and after 10 treatments of NK cell therapy, the largest tumor of has shrunk to 1/3;
chemotherapy 21 times, and after 20 treatments of NK cell therapy, the largest tumor of basically disappeared, the tumor marker value also returned to the normal range, appetite recovered, and weight increased.
NK cells: natural "anti-cancer" warrior
NK cells, also known as natural killer cells (natural killer cells), are important immune cells in the body and can kill tumor cells nonspecifically directly. This natural killer activity is not restricted by MHCh, does not rely on antibodies, and does not require antigen sensitization.
not only has the powerful killing function of , but also has a strong immune regulation function, interacting with other immune cells of the body, regulating the body's immune status and immune function .
In view of the mechanism of action of NK cells itself, in tumor immunotherapy , the following mechanisms are mainly used to encourage NK cells to play the greatest role:
. Perforin/ Granzyme kills tumors: NK cells directly release perforin and granzyme and other cytotoxic particles through exocytosis of , and activate the caspase pathway to induce the apoptosis of target cells;
. Fas/FasL pathway mediates tumor apoptosis : NK cells initiate target cell apoptosis switch through the binding of programmed death receptor ligands, mediating target cell apoptosis.
. Cytotoxicity kills tumors : NK cells exert killing effects through antibody-dependent cell-mediated cytotoxicity (ADCC), and IL-2 and IFN-γ significantly enhance the NK cell-mediated ADCC effect.
. Secretion of cytokine regulates immunity : activated NK cells can synthesize and secrete a variety of cytokines, exerting the role of regulating immunity and hematopoietic effects and directly killing target cells.
These effector functions are the key modes of NK cells for killing tumor cells, providing potential treatments for cancer.
On April 13, 2021, Celularity announced that its NK cell therapy CYNK-001 has won the title of "orphan drug" of US Food and Drug Administration (FDA), which is mainly used for the treatment of glioblastoma .
At present, countries with leading medical standards such as the United States, Japan, and Germany have made breakthrough progress in cancer NK cell therapy. A number of NK cell clinical studies have also been conducted in China and have shown good results.
Lung cancer: NK+PD-1As the king
Domestic research shows that NK cells combined with PD-1 inhibitors can double the effect and have good safety.
study showed that the objective response rate of NK cells combined with PD-1 inhibitor pemblumbab in treating non-small cell lung cancer reached 36.5%, which was nearly doubled compared with the objective response rate of 18.5% treated with pemblumbab alone!
At the same time, the number of NK cells in the patient's body increased significantly, and the level of tumor marker such as circulating tumor cells (CTC) decreased significantly, and the overall survival was significantly extended, and the safety and tolerance were good.
Breast cancer: Disease control rate 78%!
Results reported at the 2019 San Antonio breast cancer seminar included 9 triple-negative breast cancer patients, and the combination of allogeneic NK cell reflux and PD-L1 antibody drug treatment was used for treatment. achieved a disease control rate of 78% and a total response rate of 67%. At the same time, 2 patients achieved complete remission lasting 8 to 11 months. The median progression-free survival of all patients in the
trial was 13.7 months, far exceeding the 3 months of patients with triple-negative breast cancer in historical controls. At the same time, no serious adverse reactions occurred in the trial, indicating good tolerant treatment.
hepatoma: Accurate treatment, control rate of 71.4%
A domestic study evaluating HANK cells for treating liver cancer patients showed that highly active NK cells have significant efficacy and good safety for liver cancer;
The peripheral blood of the patient himself or his relatives was collected, and in vitro culture induces the production of highly active NK (HANK) cells. Intravenous infusion was performed on days 14, 15 and 16, and three consecutive infusions were performed as one course of treatment, and each patient received at least one course of treatment.
Results showed that after HANK cells, 17 patients with liver cancer achieved partial remissions of 2 cases and 8 cases were stable; the response rate of was 14.3%, and the disease control rate was 71.4%. During the treatment, no adverse reactions occurred in 17 patients.
pancreatic cancer: overall survival increase
019, the 38th JP At the Morgan Medical and Health Conference, it was reported that PD-L1.t-haNK combined with N-803 therapy had significant effect in the treatment of metastatic pancreatic cancer; 12 patients who received treatment with
, the first 10 patients achieved partial remission, and the tumor metastasis in and patients had completely subsided, and the complete remission was confirmed.
median overall survival has more than doubled (median OS: 8 months vs 3 months).
A single-arm phase 2 trial was launched in October 2020. Among the 18 second- or multi-line pancreatic cancer patients enrolled, 15 (83%) are still alive today.
leukemia : CAR-NK has more potential
CAR technology is a perfect fusion of genetic engineering and immunotherapy. The modified immune cells are like missile equipped with infrared guidance function, which can recognize tumor cells and achieve precise killing.
CAR-NK cells embed markers on NK cells so that they can accurately identify cancer cells; and NK cells will not release a large amount of inflammatory proteins, avoiding cytokine storm .
In June 2018, a new study published in the journal Cell Stem Cell said that although CAR-NK cells derived from inducing pluripotent hepatocytes (iPSCs) showed similar activities as CAR-T cells, they had lower toxicity and better anti-tumor effects.
In 2019, the University of Texas M.D. Anderson Cancer Center announced the first CAR-NK therapy in the United States to treat patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) in the journal NEJM.
study showed that among the 111 patients in , 8 patients responded to treatment, and 7 of them were completely remission, which means that they showed no signs of disease at the median follow-up of 13.8 months. The response to CD19 CAR NK cell therapy was obvious within 1 month after infusion, and the durability of this treatment was confirmed within 1 year after infusion. Lymphoma : The objective response rate reaches 100% At the 2021 AACR conference, the MD Anderson Cancer Center in the United States announced the results of a trial of umbilical blood-derived natural killer (cbNK) cells combined with innate cell conjugate (ICE®) AFM13 (CD16A/CD30) in the treatment of lymphoma. The four patients with relapsed/refractory CD30-positive lymphoma who were admitted to the group received various therapies, but the results were not ideal. Then these patients began to receive AFM13 combined with cbNK cells. All four patients responded strongly and the lesions were significantly reduced, including two complete remissions and two partial remissions. The overall objective response rate was 100%;
NK cells Five major advantages:
. Indications broad : NK cells have broad-spectrum anti-tumor effects and have been widely used in various cancers, such as hematologic tumors, neuroblastomas, ovarian tumors , rhabdomyosarcoma , breast cancer, gastric cancer, etc.
. Accurate anti-cancer : NK cells provide "off-the-shelf" immunotherapy, such as CAR-NK enhances NK cell activity, effectively reduces the inhibition of NK cells, has better anti-tumor effects, and there is almost no cytokine storm.
. Strong anti-relapse : For the clearance of residual tumor cells after surgery, for anti-relapse and metastasis treatment after surgery, it has more significant efficacy in combination with chemotherapy.
. Fast action : NK cells "kill enemies" quickly, and can annihilate cancer cells, bacteria and virus-infected cells within 5 minutes, and at the same time activate phagocytosis cells, increase its ability to clean tumors and effectively protect our bodies from damage.
5. Combined with synergistic : Strengthen the therapeutic effect of chemoradiotherapy, increase the sensitivity and killing rate of chemoradiotherapy to cancer cells, and at the same time reduce the side effects of chemoradiotherapy and improve the body's immunity.
As scientists continue to explore the anti-cancer potential of NK cells, in the future, NK cells will become a widely used method for cancer treatment like T cells, and cancer patients will also have more and more treatment options.
The 21st century is destined to be the era of cell therapy, and the best doctor is his own immunity.
