Liver cancer is the most famous "cancer of the poor" because it is high in developing countries, especially In China. According to statistics, the incidence and death of primary liver cancer in China account for 54.6% and 53.9% of the world, respectively, it is no exaggeration to say that China basically claims more than 50% of liver cancer patients with 20% of the world's population.
In February 2021, in just 1 month, first there was the "Send You a Little Red Flower" singer Zhao Yingjun died of liver cancer at an early age, and then the famous Hong Kong comedy master Wu Mengda died of ineffective liver cancer treatment, and could not help but sigh that liver cancer was so close to us.
In fact, in addition to the two of them, there are also familiar Hong Kong actor Shen Dianxia, mainland actor Fu Biao, and poet Wang Guozhen, all of whom have lost their lives by liver cancer!
About 344,000 people die of liver cancer in China every year, accounting for 55% of the world's liver cancer deaths, and one person will die of liver cancer every minute or so. Compared with the high mortality rate, the proportion of early liver cancer detection is very low, more than 90% of which is already advanced once it is found, and the opportunity for surgical treatment has been lost at this time, resulting in a 5-year survival rate of only 12%, and the 5-year survival rate of patients with advanced liver cancer is as low as 3%.
It should be emphasized that liver cancer in China and European and American countries is different!
First of all, the pathogenesis and molecular biology of liver cancer in China are very different from those in Europe and the United States, which is academically called "high heterogeneity". For example, liver cancer in China is mainly related to hepatitis B virus, while foreign countries are mainly caused by hepatitis C and other non-hepatitis virus factors (alcohol consumption, obesity, etc.).
So why is liver cancer in China so difficult to treat? The overall survival rate has not been high?
Liver cancer patients are more special, not only suffering from liver cancer, but also underlying liver disease (such as viral hepatitis, cirrhosis, liver dysfunction, etc.), so it is necessary to control the tumor and control the underlying liver disease.
High-risk groups do not have the habit of undergoing regular physical examinations and do not have early detection.
Research on new drugs and new technologies is scarce.
Patients with advanced liver cancer generally do not have the value of surgical transplantation, and cellular immunotherapy can help patients improve the body's immunity, while there is a strong lethality for tumor cells, which is a new treatment method for malignant tumors.
As the "fourth therapy" after surgery, radiotherapy and chemotherapy, the clinical research of cellular immunotherapy in liver cancer has never stopped in recent years, which is expected to break the "shackles" of Chinese liver cancer patients for many years!
Behind the death of Wu Mengda Zhao Yingjun due to liver cancer, immune cell therapy may become the last killer to overcome liver cancer!
CAR-T therapy
CAR-T therapy is chimeric antigen receptor T cell immunotherapy, which is a new type of precision targeted therapy for the treatment of tumors. Through genetic engineering technology, T cells are activated and equipped with a positioning navigation device CAR (tumor chimeric antigen receptor), which transforms the ordinary "warrior" of T cells into a "super soldier", that is, CAR-T cells, which specifically recognize tumor cells in the body and efficiently kill tumor cells, so as to achieve the purpose of treating malignant tumors.
At present, with the approval of Agironse injection and Ricky Olense injection in China before and after, the field of cancer treatment has quickly set off a "CAR-T fever". Current clinical trial targets for car-T in the treatment of liver cancer are mainly GPC3 (phosphatidyl inositol protein polysaccharide 3).
Chinese exclusive CAR-T clinical trial and won the first battle
Phosphatidylinositol proteoglycan 3 (Glypican 3, GPC3) plays an important role in regulating cell growth and differentiation, and is closely related to the occurrence and development of liver cancer. GPC3 is highly specific in liver cancer tissues, suggesting that GPC3 has obvious sensitivity and specificity for liver cancer diagnosis, and can be used as a new target for liver cancer treatment.
Xiaobian learned another shocking news in the "China Daily" on May 13, which was jointly completed by the team of Professor Zhai Bo, director of the Department of Interventional Oncology of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and took the lead in focusing on the safety of CAR-T cell therapy. The results of a Phase I clinical study of CAR-T cell therapy for advanced hepatocellular carcinoma (HCC) targeting GPC3 were "available": the safety and efficacy of the treatment yielded promising results.
In two prospective Phase I studies, adult patients with advanced GPC3+ HCC (Child-Pugh A) received autologous CAR-GPC3 T-cell therapy after cyclophosphamide and fludarabine-induced lymph clearance. The main objective is to assess the safety of treatment.
As of July 24, 2019, a total of 13 patients received CAR-GPC3 T cells with a median value of 19.9×108. All patients were GPC3-positive, had undergone surgery, topical treatment, or systemic systemic therapy, and all carried hepatitis B virus (HBV).
Two of these patients achieved partial response (PR), with 6-month, 1-year, and 3-year survival rates of 50.3%, 42.0%, and 10.5%, respectively, and a median survival time (OS) of 278 days (39.7 weeks).
The disease control rate has reached 78%, and domestic CAR-T therapy has made great efforts in the field of liver cancer
At this year's ASCO Annual Meeting, Chinese medical researchers for the first time released the latest clinical research data on car-T drugs (Ori-CAR-001) targeting GPC3 for the treatment of relapsed/refractory hepatocellular carcinoma. Preliminary data from the study showed that Ori-CAR-001 showed good safety and efficacy in GPC3-positive relapsed/refractory patients.
As of March 10, 2021, a total of 11 relapsed subjects who received cell infusions were enrolled. All subjects had advanced hepatocellular carcinoma and were ineffective after chemotherapy, TACE (hepatic artery chemoembolization), and targeted therapy. Of the 9 assessable subjects, 4 achieved partial remission (PR), 3 achieved disease stabilization (SD), and 2 developed disease progression (PD), with an objective response rate of 44% and a disease control rate of 78%.
Typical cases
The internationally renowned journal Journal of Hematology & Oncology published a clinical study by Chinese medical researchers to successfully transform CAR-T technology, and the target of CAR-T product selection mentioned in the study was glypican-3 (GPC3, mainly liver cancer).
One of the patients with advanced liver cancer received intratumoral CAR-T injection, and the metabolism of liver lesions basically disappeared after treatment.
Although the size of the 2 lung nodules did not change significantly after 60 days of CAR-T cell injection, the liver tumor lesion (1.2×1.3 cm) contracted significantly on day 10, and the GPC3-7 × 19 CAR-T cells completely disappeared after 32 days.
Patients did not have any toxic effects and were assessed in stages according to the standard Solid Tumor Response Assessment Criteria (RECIST) version 1.1 on CT, showing partial remission (PR).
Car-T clinical trials of a variety of hematological tumors and solid tumors are being recruited in Cancer-free Home, and interested parties can consult the Medical Department for specific assessments!
TCR-T therapy
BOTH CAR-T cells and TCR-T cells are genetically engineered T cells. Compared with CAR-T therapy, TCR-T therapy has unique advantages in the field of solid tumor treatment.
TCR-T cell therapy can recognize tumor-specific antigens from the surface of cell membranes or intracellular sources, and has entered clinical application from the very beginning of basic immune research, showing initial efficacy in solid tumors, becoming the most likely T cell immunotherapy to make breakthroughs in the field of solid tumors!
What is TCR-T Cell Therapy?
The main mechanism of TCR-T technology is to introduce new genes into ordinary T cells so that the modified T cells can express TCRs (T cell receptors) that effectively recognize tumor cells, thereby guiding T cells to kill tumor cells.
Advanced liver cancer ushers in a new dawn! TCR-T therapy allows complete remission in cancer patients
As early as the 2020 International Conference on Liver Disease (ILC), a new TCR-T therapy for liver cancer based on T cells, ADP-A2AFP, caused quite a stir and made new breakthroughs in new therapies for liver cancer.
Of the included patients, one patient showed complete remission (CR) in cancer cell progression, and the remaining participants also experienced varying degrees of decline in alpha-fetoprotein (AFP), which means that the trial has progressed and that the therapy is effective in the treatment of advanced liver cancer.
All 9 patients who participated underwent surgery and conventional chemoradiotherapy, but experienced failure or intolerance. Of the 4 patients who received the highest dose of treatment, 1 patient achieved complete remission, and the CT scan showed that all lesions in the patient's body disappeared, and the complete remission lasted for more than half a year without any recurrence!
The best response of other patients (cohort 1, cohort 2) was stabilization. One patient in cohort 2 did not shrink in the primary lesion volume after 1 month of treatment, but the volume of the mediastinal lymph node metastases decreased significantly!
Therefore, TCR-T therapies targeting AFP (alpha-fetoprotein) are able to kill AFP-expressing tumor cells, and based on the positive results of this study, the researchers are expected to expand the maximum dose to 5 billion cell therapies, and we look forward to the publication of updated data for this study!
Cancer-free home TCR-T therapy recruitment
So is there a chance to try TCR-T therapy? This brings a good news, there is currently a research and development of TCR-T therapy in the recruitment of liver cancer patients to carry out clinical trials, patients who want to participate can consult the Cancer-free Home Medical Department for detailed entry criteria.
【Some of the selection criteria are as follows】
1. 18 years old≤ age ≤ 70 years old, both men and women;
2. Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology, who are not suitable for surgery or topical therapy and who have progressed or are intolerant after receiving at least one normative systemic therapy (systemic therapy includes but is not limited to systemic chemotherapy, molecular targeting, immune checkpoint inhibitors, etc.), or who are unable to undertake standard therapy;
Genotype screening must be in accordance with: HLA-A*02:01, 02:02, 02:03, 02:04, 02:07, 02:09 or 02:16.
Treatment of tumor-infiltrating lymphocytes (TIL).
TILs therapy, simply put, is to isolate and purify the lymphocytes in the surgically removed tumor tissue, select the lymphocytes that can specifically fight cancer, expand and activate and then infusion. This type of therapy has a history of more than 30 years, the earliest used for malignant melanoma, in recent years in cervical cancer, lung cancer and other solid tumors have given a good data.
This therapy is equivalent to directly pulling back veterans with combat experience from the battlefield, and after a round of "political review" and "big competition" of professional ability, the traitors and traitors are eliminated as much as possible, leaving the most effective ones to provide supplies, and then sending them back to the battlefield to continue fighting.
Disease control rate 89%! LN-145 Therapy Awarded FDA Breakthrough Therapy!
In June 2019, the FDA approved the tumor invasive lymphocyte (TIL) treatment method LN-145 as a breakthrough treatment designation, which is the first time that the cellular immunotherapy for solid tumors has won this award, and it is believed that it is only a matter of time before it is marketed, and once approved by the FDA, it will be the first cellular immunotherapy for solid tumors, which will bring huge survival benefits to cancer patients.
The FDA award is based on data from the ongoing phase II innovaTIL-04 (C-145-04) aggressive trial, which summary data shows that the overall response rate (ORR) to TIL treatment in patients with advanced cervical cancer is 44% and the disease control rate is 89%!
New Hope for Advanced Liver Cancer! The world's first report on the clinical efficacy of autologous TILs therapy technology is gratifying!
Recently, the Journal of Clinical Surgery published online clinical trials of DOMESTIC SCHOLARS ON TILs therapy technology in advanced liver cancer, and observed good safety and efficacy. TILs are a type of adoptive cell therapy that falls into two categories: no-screening TILs and screening-based TILs. With the inhibition of tumor immune evasion mechanism by anti-PD-1 therapy, tumor killer cells represented by lymphocytes may exert better killing effects on tumors. TILs combined with anti-PD-1 therapy will theoretically exert a more effective synergistic killing effect on tumor cells, which is expected to become a new model of immune combination therapy with significant therapeutic prospects.
In 2019, the domestic research team designed a clinical trial of TILs cell therapy combined with immune checkpoint inhibitor therapy. The trial selected patients with liver cancer whose recurrence after surgery could not be radically resected or who were accompanied by extrahepatic metastases as study subjects. Amplified TILs were isolated from the resected tumor and autologous infusion was performed, and their initial efficacy was observed after infusion in combination with anti-PD-1 monoclonal antibody.
In the four clinical trials currently underway, the in vitro expansion and infusion of TILs in 3 patients with advanced hepatocellular carcinoma and 1 patient with intrahepatic bile duct carcinoma were successful, and the maximum expansion increase of TILs reached 3.5×10^10 cells. Among the 4 patients, only 1 patient had a grade I adverse reaction, and 4 patients did not have a grade III/IV serious adverse reaction before and after cell injection. At present, the follow-up time of these two patients with advanced liver cancer has exceeded 1 year.
This is the first time at home and abroad that a significant effect has been observed in advanced liver cancer using immune checkpoint inhibitors combined with adoptive immunotherapy. Studies have shown that the back-infusion of TILs after in vitro amplification combined with anti-PD-1 monoclonal antibody therapy may become a new treatment for liver cancer.
TILs immunotherapy recruitment
At present, a TILs immune cell clinical trial is being recruited in the cancer-free home, which mainly treats malignant solid tumors (including lung cancer, esophageal cancer, ovarian cancer, cervical cancer, breast cancer) and other cancers.
If you would like to attend, please consult the Cancer Free Home Medical Department for a detailed assessment of your condition.
Prevention and treatment of liver cancer focuses on prevention, and early cancer screening should be put on the agenda!
In addition to the new hope of cellular immunotherapy for the treatment of advanced liver cancer, early cancer screening for liver cancer should be on the agenda!
In the early stage of liver cancer, there are no obvious symptoms, but liver disease itself is a very clear early indication! Studies have shown that liver cancer is related to hepatitis B, hepatitis C, alcoholic hepatitis and other hepatitis, and liver cancer is not achieved overnight, hepatitis - cirrhosis - liver cancer trilogy, I believe everyone has heard about it.
Although liver cancer does not expose too many clues in the early stages, people with liver disease need to be vigilant against symptoms of spider angioma, liver pain, digestive decline, and jaundice. The specific items of early cancer screening for liver cancer are attached below, as shown in the figure:
The editor has something to say
Finally, the small editor of the cancer-free home should warn all cancer friends not to miss any opportunity for treatment to prolong survival.
Because the causes of liver cancer are particularly complex, in order to further improve the effect of liver cancer treatment, it is necessary to use "combination fists", that is, targeted therapy, immunotherapy, proton therapy, etc. In addition, in how to choose the best treatment plan and medication should turn to authoritative experts at home and abroad, so that the majority of cancer friends can take fewer detours and get the greatest clinical benefits.