Immunotherapy has become a new hope for mankind to fight cancer, and CAR-T therapy is one of the most promising tumor immunotherapies in recent years. This technology has made great progress in the treatment of various malignancies and has been successfully used in the treatment of a variety of hematological malignancies.
On December 12, 2022, according to "News Medical Life Sciences", Great Ormond Street Hospital and University College London announced early clinical data of universal CAR-T cell therapy developed based on base editing technology for the treatment of acute T lymphoblastic leukemia (T-ALL).
Screenshot from the official website of "News Medical Life Sciences"
In this trial, a 13-year-old girl Alyssa from Leicester, England, was the first in the world to receive CAR-T cell therapy modified by base editing. After 28 days of treatment, her condition was in remission and she continued to receive a bone marrow transplant to restore immune system function. Fortunately, 6 months later, the patient's body recovered well and the cancer cells were no longer detectable!
Alyssa was diagnosed with acute T-lymphoblastic leukemia in 2021, but relapsed after undergoing chemotherapy and a bone marrow transplant. Acute T-lymphoblastic leukemia accounts for more than 70% of childhood leukemias, but treatment methods are very limited, mainly chemotherapy and hematopoietic stem cell transplantation.
The tricky thing is that because of the cancerous T cells in her body, she needs to use gene editing to modify the CAR-T cells to attack the cancerous T cells instead of attacking each other.
According to the official website, this is the world’s first clinical study of a universal cell therapy based on base editing entering the human body. The experimental therapy that Alyssa received this time is called BE CAR7-T cell therapy. This is a universal CD7 CAR-T cell therapy that knocks out of three genes. Its biggest breakthrough is that has truly verified that base editing can design CAR-T cells more accurately and safely.
doubles the anti-cancer effect! "Work hard" on various modifications of CAR-T therapy to help conquer solid tumors!
However, for hematological tumors with relatively mature development of cellular immunotherapy, solid tumors should be the "main battlefield" in the fight against cancer! Although it is the main battlefield, the development of cellular immunotherapy in the vast field of solid tumors is stretched and difficult. As the latest global cancer data in 2021 points out, about 90% of cancer incidence is caused by solid tumors. However, there are very few clinical trials of cell therapy for solid tumors ( solid tumors account for 40%, and most of them are in early stages). It can be seen that solid tumors are still a difficulty in cellular immunotherapy.
Although there are multiple difficulties on the road to fighting solid tumors, CAR-T therapy has made outstanding progress in gastric cancer , liver cancer , pancreatic cancer and other fields in recent years. Scholars at home and abroad have made various modifications to CAR-T and continue to discover new targets for the treatment of various solid tumors.
Today, the editor of Cancer-Free Home will give you a general introduction to the various modifications made by domestic and foreign scholars on CAR-T therapy, so that everyone can understand the cutting-edge research related to the development of CAR-T products for the treatment of solid tumors by medical researchers, and what progress and breakthroughs they have made.
gene was transferred to prepare "super CAR-T cells", which quadruples the anti-cancer effect!
On March 5, 2018, the CAR-T field ushered in a major research development.A foreign research team has successfully developed a new generation of CAR-T. By transferring interleukin 7 (IL-7) and chemokine CCL19 genes into CAR-T cells, they have produced "super CAR-T cells" that can effectively kill tumors, allowing almost 100% survival of mice with tumors!
Fortunately, the above-mentioned preclinical experiment idea has been realized in humans! In response to problems such as the difficulty of CAR-T cells entering tumor tissue and the fact that CAR-T cells are easily blocked by other immunosuppressive molecules or cells after entering tumor tissue and cannot function, Chinese medical researchers have come up with a way to make CAR-T cells secrete cytokines and chemokines at the same time. These factors are like equipping CAR-T cells with their own energy motors, which can enhance the ability of CAR-T cells to enter tumors.
On July 29, 2021, the internationally renowned magazine "Journal of Hematology & Oncology" published a clinical study by Chinese medical researchers on the successful transformation of CAR-T technology. The targets of the CAR-T products mentioned in the study are glypican-3 (GPC3, mainly liver cancer) and mesothelin (MSL). N, also known as mesothelin, can be applied to a variety of epithelial cancers, such as malignant mesothelioma, pancreatic cancer, gastric cancer, ovarian cancer, etc.) . In order to make CAR-T cells have a stronger ability to enter the tumor, the researchers specially added interleukin 7 (IL-7) and the chemokine CCL19.
This study included 6 patients with advanced hepatocellular carcinoma (HCC), pancreatic cancer (PC) and ovarian cancer (OC) with GPC3 or MSLN expression. The results of the treatment were amazing!
Among them,
What’s even more amazing is that
is currently urgently recruiting B-cell lymphoma, T-cell lymphoma, T-cell leukemia (T-ALL), acute lymphoblastic leukemia, non-Hodgkin lymphoma, liver cancer, pancreatic cancer, colorectal cancer, mesothelioma, ovarian cancer and other cancer types!
If you want to evaluate whether your condition is suitable for CAR-T therapy, you can submit your pathology report, treatment experience and discharge summary, etc. to Cancer Free Home Medical Department 4006269916 for preliminary evaluation!
innovative cellular immune combination! Using mRNA vaccines to improve the efficacy of CAR-T
BNT211 developed by BioNTech is a new generation of CAR-T therapy targeting solid tumors. It combines CAR-T therapy targeting the CLDN6 antigen with CARVac, an mRNA vaccine expressing the CLDN6 antigen. It is worth mentioning that at the 2022 ESMO Conference, researchers will announce the latest clinical trial data of BNT211.
This ongoing clinical trial is the world’s first attempt to use an mRNA vaccine to enhance CAR-T cell function and the first cell therapy to target CLDN6.
A total of 22 patients were included in this trial (21 of whom were evaluable for efficacy). Tumor indications included testicular cancer (n = 13), ovarian cancer (n = 4), endometrial cancer (n = 1), fallopian tube cancer (n = 1), sarcoma (n = 1), gastric cancer (n = 1), and 1 tumor of unknown primary origin.
As of August 16, 2022, the efficacy evaluation of 21 evaluable patients showed that the best overall response rate was 33% and the disease control rate was 67%, including 11 patients with complete response (CR), 6 patients with partial response (PR) and 7 patients with stable disease (SD).
Immunotherapy has become a new hope for mankind to fight cancer, and CAR-T therapy is one of the most promising tumor immunotherapies in recent years. This technology has made great progress in the treatment of various malignancies and has been successfully used in the treatment of a variety of hematological malignancies.
On December 12, 2022, according to "News Medical Life Sciences", Great Ormond Street Hospital and University College London announced early clinical data of universal CAR-T cell therapy developed based on base editing technology for the treatment of acute T lymphoblastic leukemia (T-ALL).
Screenshot from the official website of "News Medical Life Sciences"
In this trial, a 13-year-old girl Alyssa from Leicester, England, was the first in the world to receive CAR-T cell therapy modified by base editing. After 28 days of treatment, her condition was in remission and she continued to receive a bone marrow transplant to restore immune system function. Fortunately, 6 months later, the patient's body recovered well and the cancer cells were no longer detectable!
Alyssa was diagnosed with acute T-lymphoblastic leukemia in 2021, but relapsed after undergoing chemotherapy and a bone marrow transplant. Acute T-lymphoblastic leukemia accounts for more than 70% of childhood leukemias, but treatment methods are very limited, mainly chemotherapy and hematopoietic stem cell transplantation.
The tricky thing is that because of the cancerous T cells in her body, she needs to use gene editing to modify the CAR-T cells to attack the cancerous T cells instead of attacking each other.
According to the official website, this is the world’s first clinical study of a universal cell therapy based on base editing entering the human body. The experimental therapy that Alyssa received this time is called BE CAR7-T cell therapy. This is a universal CD7 CAR-T cell therapy that knocks out of three genes. Its biggest breakthrough is that has truly verified that base editing can design CAR-T cells more accurately and safely.
doubles the anti-cancer effect! "Work hard" on various modifications of CAR-T therapy to help conquer solid tumors!
However, for hematological tumors with relatively mature development of cellular immunotherapy, solid tumors should be the "main battlefield" in the fight against cancer! Although it is the main battlefield, the development of cellular immunotherapy in the vast field of solid tumors is stretched and difficult. As the latest global cancer data in 2021 points out, about 90% of cancer incidence is caused by solid tumors. However, there are very few clinical trials of cell therapy for solid tumors ( solid tumors account for 40%, and most of them are in early stages). It can be seen that solid tumors are still a difficulty in cellular immunotherapy.
Although there are multiple difficulties on the road to fighting solid tumors, CAR-T therapy has made outstanding progress in gastric cancer , liver cancer , pancreatic cancer and other fields in recent years. Scholars at home and abroad have made various modifications to CAR-T and continue to discover new targets for the treatment of various solid tumors.
Today, the editor of Cancer-Free Home will give you a general introduction to the various modifications made by domestic and foreign scholars on CAR-T therapy, so that everyone can understand the cutting-edge research related to the development of CAR-T products for the treatment of solid tumors by medical researchers, and what progress and breakthroughs they have made.
gene was transferred to prepare "super CAR-T cells", which quadruples the anti-cancer effect!
On March 5, 2018, the CAR-T field ushered in a major research development.A foreign research team has successfully developed a new generation of CAR-T. By transferring interleukin 7 (IL-7) and chemokine CCL19 genes into CAR-T cells, they have produced "super CAR-T cells" that can effectively kill tumors, allowing almost 100% survival of mice with tumors!
Fortunately, the above-mentioned preclinical experiment idea has been realized in humans! In response to problems such as the difficulty of CAR-T cells entering tumor tissue and the fact that CAR-T cells are easily blocked by other immunosuppressive molecules or cells after entering tumor tissue and cannot function, Chinese medical researchers have come up with a way to make CAR-T cells secrete cytokines and chemokines at the same time. These factors are like equipping CAR-T cells with their own energy motors, which can enhance the ability of CAR-T cells to enter tumors.
On July 29, 2021, the internationally renowned magazine "Journal of Hematology & Oncology" published a clinical study by Chinese medical researchers on the successful transformation of CAR-T technology. The targets of the CAR-T products mentioned in the study are glypican-3 (GPC3, mainly liver cancer) and mesothelin (MSL). N, also known as mesothelin, can be applied to a variety of epithelial cancers, such as malignant mesothelioma, pancreatic cancer, gastric cancer, ovarian cancer, etc.) . In order to make CAR-T cells have a stronger ability to enter the tumor, the researchers specially added interleukin 7 (IL-7) and the chemokine CCL19.
This study included 6 patients with advanced hepatocellular carcinoma (HCC), pancreatic cancer (PC) and ovarian cancer (OC) with GPC3 or MSLN expression. The results of the treatment were amazing!
Among them,
What’s even more amazing is that
is currently urgently recruiting B-cell lymphoma, T-cell lymphoma, T-cell leukemia (T-ALL), acute lymphoblastic leukemia, non-Hodgkin lymphoma, liver cancer, pancreatic cancer, colorectal cancer, mesothelioma, ovarian cancer and other cancer types!
If you want to evaluate whether your condition is suitable for CAR-T therapy, you can submit your pathology report, treatment experience and discharge summary, etc. to Cancer Free Home Medical Department 4006269916 for preliminary evaluation!
innovative cellular immune combination! Using mRNA vaccines to improve the efficacy of CAR-T
BNT211 developed by BioNTech is a new generation of CAR-T therapy targeting solid tumors. It combines CAR-T therapy targeting the CLDN6 antigen with CARVac, an mRNA vaccine expressing the CLDN6 antigen. It is worth mentioning that at the 2022 ESMO Conference, researchers will announce the latest clinical trial data of BNT211.
This ongoing clinical trial is the world’s first attempt to use an mRNA vaccine to enhance CAR-T cell function and the first cell therapy to target CLDN6.
A total of 22 patients were included in this trial (21 of whom were evaluable for efficacy). Tumor indications included testicular cancer (n = 13), ovarian cancer (n = 4), endometrial cancer (n = 1), fallopian tube cancer (n = 1), sarcoma (n = 1), gastric cancer (n = 1), and 1 tumor of unknown primary origin.
As of August 16, 2022, the efficacy evaluation of 21 evaluable patients showed that the best overall response rate was 33% and the disease control rate was 67%, including 11 patients with complete response (CR), 6 patients with partial response (PR) and 7 patients with stable disease (SD). This means that more than 60% of patients have stable disease control or a significant reduction of more than 30%, or even disappear completely!
It is particularly worth mentioning that the second dose group of this combination therapy showed a stronger anti-cancer effect in patients with testicular cancer accompanied by lymphatic failure (n=7). The objective response rate was as high as 57%, and the disease control rate was as high as 85%.
At the time the study data were collected, a patient with testicular cancer who had previously received six lines of chemotherapy was still in sustained complete remission . The researchers pointed out that this was a patient with a large tumor mass at baseline who showed impressive tumor regression after 6 weeks of CAR-T cell treatment. At only 112 weeks, all metastases in the lungs disappeared, and the evaluation reached a state of complete remission.
Treatment situation of typical patients with testicular cancer
In summary, the results of the BNT211 clinical trial have preliminarily confirmed that CLDN6 CAR-T cell combined with CAR-T RNA vaccine (CARVac) showed good safety and encouraging efficacy in the dose exploration phase. The mRNA vaccine (CARVac) can be used to improve the anti-tumor effect of CAR-T cells, providing a new strategy for using CAR-T cells to treat refractory solid tumors.
breakthrough! New CAR-T cells for solid tumors only kill cancer cells and do not damage normal tissues.
On March 21, 2022, Chinese scholars and their research team at the Perelman School of Medicine at the University of Pennsylvania discovered a new tumor antigen CDH17, which was a tumor antigen identified from a nanobody derived from llama . It is worth mentioning that CDH17 is expressed in both tumor tissues and healthy tissues, but CAR-T cells targeting CDH17 only kill cancer cells and will not harm normal tissues because CDH17 is isolated and hidden among normal cells. This study even involved Carl June, the “father of CAR-T”!
The results of this study, the first to target CDH17 in neuroendocrine tumors , show that CAR-T cells in tumors are exposed to a new class of tumor-associated antigens but are sequestered from CAR-T cells in healthy tissue.
All in all, the research results are of great clinical reference value. This study shows that CDH17 is a potential target for neuroendocrine tumors, gastrointestinal cancers and other CDH17-expressing solid tumors, and is expected to be further developed as adoptive immunotherapy.
targets solid tumors! Domestic CAR-T therapy has accumulated a lot of experience and is at full strength! !
The key point of CAR-T therapy for solid tumors is the selection of solid tumor targets. The distribution of targets involved in CAR-T projects currently under clinical development, taking the latest global cancer data in 2022 as an example, is mainly concentrated on popular targets such as GPC3, Claudin18.2, MSLN, HER2, EGFR.
Gastric cancer and pancreatic cancer: target Claudin18.2
As the world’s first CAR-T cell targeting Claudin18.2, CT041 has amazed the world since its debut in 2019. Its remarkable efficacy shows good treatment prospects for digestive system tumors.
On May 9, 2022, the research results of Keji Pharmaceutical's CAR-T cell product CT041 in the treatment of digestive system tumors were published in the top international journal "Nature Medicine". This is also the first clinical study with the largest sample size to date of CAR-T cell treatment of solid tumors published in the top academic journal !
Research data shows
. For gastric cancer patients who have failed at least 2 lines of treatment in the past: the objective response rate is
61.1%, and the disease control rate is 83.3%.
In addition, there are a variety of CAR-T cell therapies targeting CLDN18.2. For example, LB-1904, developed by Legend Biotech, is used to treat gastric cancer or pancreatic cancer and has entered Phase I clinical trials. In addition, there are a number of clinical trials targeting Claudin18.2 in my country that are currently recruiting for clinical trials.
Liver cancer: target GPC3 (phosphatidylinositol proteoglycan 3)
On August 18, 2022, Keji Pharmaceutical announced that the magazine "Frontiers in Immunology" published a long-term survival case report on its independently developed GPC3-targeting CAR-T cell candidate product CT011 in the treatment of advanced hepatocellular carcinoma.
This study reported that
This is a 60-year-old man with hepatitis B virus (HBV)-related hepatocellular carcinoma. Treatment with CT011 combined with sorafenib was well tolerated. The patient achieved partial response (PR) starting at month 3 and complete response at month 12 after the first cycle of CT011 infusion. The tumor had not progressed for more than 36 months (over 3 years) and remained in complete remission for more than 24 months after the first infusion.
Colorectal Cancer: Target GCC/GUCY2C
On April 19, 2022, Shanghai Stansey Bio announced that its developed solid tumor CAR-T product GCC19CART was granted fast track status by the U.S. Food and Drug Administration (FDA).
At the ASGCT meeting, Stansey introduced the latest clinical data on 21 patients, of which 13 patients were enrolled at the level 1 dose (1x106 cells/kg) and 8 patients were enrolled at the level 2 dose (2x106 cells/kg).. According to the Response Evaluation Criteria for Solid Tumors (RECIST1.1), the objective response rate (ORR) in the level 1 dose group was 15.4% (2/13), and the objective response rate (ORR) in the html level 12 dose group was 50% (4/8).
In addition to the target GCC, another effective target in colorectal cancer, GUCY2C, is also a hot topic in recent research. China has a small CAR-T study on 7 patients, targeting the colon cancer marker GUCY2C. The study found that 2 to 3 patients experienced partial remission and stable disease.
Mesothelioma, ovarian cancer, pancreatic cancer: target MSLN
In November 2021, medical researchers from the United States released the phase I results of a clinical trial of CAR-T combined with PD-1 inhibitors in the well-known "Cancer Discovery" magazine mainly describes the clinical efficacy of autologous CAR-T cells targeting mesothelin in combination with pembrolizumab (trade name Keytruda) in the treatment of malignant pleural mesothelioma (MPM).
Mesothelin is highly expressed in a variety of tumor tissues, such as pancreatic cancer, ovarian cancer, breast cancer, endometrial cancer, prostate cancer and cholangiocarcinoma (image source PNAS)
In this clinical trial, a total of 27 patients with thoracic tumors were included in the treatment, including 1 case of metastatic lung adenocarcinoma, 1 case of metastatic breast cancer, and the rest were patients with malignant pleural mesothelioma.
html Among the 127 patients, 23 patients with malignant pleural mesothelioma received cyclophosphamide pretreatment before CAR-T treatment. Among them, 18 patients received CAR-T combined with pembrolizumab treatment, and 5 patients received CAR-T treatment alone. It is worth mentioning that all patients in had received one round of previous treatment, and 33% of patients had received ≥3 rounds of previous treatment.
It should be pointed out that malignant pleural mesothelioma is a malignant tumor with low PD-L1 expression and tumor mutation load. Early clinical trials also proved that patients cannot benefit from PD-1/PD-L1 immunosuppressant monotherapy.
The average interval from diagnosis to receipt of CAR-T treatment for the enrolled patients was 6.1 months, and the average interval from CAR-T treatment to the start of pembrolizumab treatment was 6 weeks. Surprisingly, researchers found no dose-limiting toxicity within the CAR-T dose range of 3×105~6×107/kg.No patient with developed grade 2 or above cytokine storm , nervous system toxicity, or off-target side effects .
On the premise of ensuring the safety and sustainability of cell products, the clinical results are also particularly amazing!
html Among 123 patients with malignant pleural mesothelioma who received treatment, the median survival time after CAR-T treatment was 17.7 months, and the one-year survival rate was 74%. Among the 18 patients who received CAR-T + pembrolizumab combination therapy, the median survival time reached 23.9 months, and the one-year survival rate was 83%.
An even more surprising finding is that CAR-T therapy targeting mesothelin is expected to achieve long-term disease remission in patients with malignant pleural mesothelioma. In the imaging examinations at 4 to 6 weeks after treatment (n=16), 12.5% of the patients achieved partial remission, and 56.3% of the patients had stable disease. Among patients with stable disease or partial response, eight patients were able to maintain their disease status for more than 6 months.
Clinical trials of CAR-T cell therapy and CAR-NK therapy targeting MSLN (mesothelin) are recruiting patients. Interested patients with mesothelioma and other solid tumors can submit pathological reports, treatment experience and hospitalization summary and other information through the Cancer-Free Home Medical Department for a preliminary evaluation of whether this therapy can be used.
There is a long way to go, and CAR-T therapy will bring new hope to more patients with solid tumors!
recently published an article on the ten-year development and clinical application of CAR-T cell therapy in the internationally renowned journal "Lancet-Hematology". It elaborates that as of November 15, 2021, 714 clinical studies of CAR-T cell therapy have been registered in China, including 510 on ClinicalTrials.gov and 204 on China clinical trial registration studies.
The number of INDs for CAR-T cell therapy in China continues to increase. 73 CAR-T cell products from 32 companies have submitted IND applications, and 36 have received implicit permission to enter clinical trials. Among them, acute lymphoblastic leukemia and non-Hodgkin lymphoma are one of the most common indications.
Among them, the domestically developed of Legend Biotech, Cedagene Biotech , GCC19CART of Stance Biotech, and Claudin18.2 CAR-T of Keji Pharmaceutical have all reached the world's leading level. In addition, many companies are deploying next-generation CAR-T and allogeneic CAR-T technologies. The preliminary data are excellent and they are expected to gain global market share.
In 2021, our country ushered in the first year of cellular immunotherapy. As a pioneer, CAR-T therapy is one of the future development directions. CAR-T therapy mainly focuses on modifying T cells to recognize special targets of tumor cells. In theory, there can be countless kinds of CAR-T therapies targeting different targets, which means there are endless possibilities.
hopes that in the near future, with the efforts of domestic and foreign medical researchers, the toxic and side effects of cell therapy can be reduced, the price can be reduced, the bottleneck of solid tumors can be broken, and more and more patients with advanced cancer can benefit!
This article is original from Cancer Free Home
In addition, there are a variety of CAR-T cell therapies targeting CLDN18.2. For example, LB-1904, developed by Legend Biotech, is used to treat gastric cancer or pancreatic cancer and has entered Phase I clinical trials. In addition, there are a number of clinical trials targeting Claudin18.2 in my country that are currently recruiting for clinical trials.
Liver cancer: target GPC3 (phosphatidylinositol proteoglycan 3)
On August 18, 2022, Keji Pharmaceutical announced that the magazine "Frontiers in Immunology" published a long-term survival case report on its independently developed GPC3-targeting CAR-T cell candidate product CT011 in the treatment of advanced hepatocellular carcinoma.
This study reported that
This is a 60-year-old man with hepatitis B virus (HBV)-related hepatocellular carcinoma. Treatment with CT011 combined with sorafenib was well tolerated. The patient achieved partial response (PR) starting at month 3 and complete response at month 12 after the first cycle of CT011 infusion. The tumor had not progressed for more than 36 months (over 3 years) and remained in complete remission for more than 24 months after the first infusion.
Colorectal Cancer: Target GCC/GUCY2C
On April 19, 2022, Shanghai Stansey Bio announced that its developed solid tumor CAR-T product GCC19CART was granted fast track status by the U.S. Food and Drug Administration (FDA).
At the ASGCT meeting, Stansey introduced the latest clinical data on 21 patients, of which 13 patients were enrolled at the level 1 dose (1x106 cells/kg) and 8 patients were enrolled at the level 2 dose (2x106 cells/kg).. According to the Response Evaluation Criteria for Solid Tumors (RECIST1.1), the objective response rate (ORR) in the level 1 dose group was 15.4% (2/13), and the objective response rate (ORR) in the html level 12 dose group was 50% (4/8).
In addition to the target GCC, another effective target in colorectal cancer, GUCY2C, is also a hot topic in recent research. China has a small CAR-T study on 7 patients, targeting the colon cancer marker GUCY2C. The study found that 2 to 3 patients experienced partial remission and stable disease.
Mesothelioma, ovarian cancer, pancreatic cancer: target MSLN
In November 2021, medical researchers from the United States released the phase I results of a clinical trial of CAR-T combined with PD-1 inhibitors in the well-known "Cancer Discovery" magazine mainly describes the clinical efficacy of autologous CAR-T cells targeting mesothelin in combination with pembrolizumab (trade name Keytruda) in the treatment of malignant pleural mesothelioma (MPM).
Mesothelin is highly expressed in a variety of tumor tissues, such as pancreatic cancer, ovarian cancer, breast cancer, endometrial cancer, prostate cancer and cholangiocarcinoma (image source PNAS)
In this clinical trial, a total of 27 patients with thoracic tumors were included in the treatment, including 1 case of metastatic lung adenocarcinoma, 1 case of metastatic breast cancer, and the rest were patients with malignant pleural mesothelioma.
html Among the 127 patients, 23 patients with malignant pleural mesothelioma received cyclophosphamide pretreatment before CAR-T treatment. Among them, 18 patients received CAR-T combined with pembrolizumab treatment, and 5 patients received CAR-T treatment alone. It is worth mentioning that all patients in had received one round of previous treatment, and 33% of patients had received ≥3 rounds of previous treatment.
It should be pointed out that malignant pleural mesothelioma is a malignant tumor with low PD-L1 expression and tumor mutation load. Early clinical trials also proved that patients cannot benefit from PD-1/PD-L1 immunosuppressant monotherapy.
The average interval from diagnosis to receipt of CAR-T treatment for the enrolled patients was 6.1 months, and the average interval from CAR-T treatment to the start of pembrolizumab treatment was 6 weeks. Surprisingly, researchers found no dose-limiting toxicity within the CAR-T dose range of 3×105~6×107/kg.No patient with developed grade 2 or above cytokine storm , nervous system toxicity, or off-target side effects .
On the premise of ensuring the safety and sustainability of cell products, the clinical results are also particularly amazing!
html Among 123 patients with malignant pleural mesothelioma who received treatment, the median survival time after CAR-T treatment was 17.7 months, and the one-year survival rate was 74%. Among the 18 patients who received CAR-T + pembrolizumab combination therapy, the median survival time reached 23.9 months, and the one-year survival rate was 83%.
An even more surprising finding is that CAR-T therapy targeting mesothelin is expected to achieve long-term disease remission in patients with malignant pleural mesothelioma. In the imaging examinations at 4 to 6 weeks after treatment (n=16), 12.5% of the patients achieved partial remission, and 56.3% of the patients had stable disease. Among patients with stable disease or partial response, eight patients were able to maintain their disease status for more than 6 months.
Clinical trials of CAR-T cell therapy and CAR-NK therapy targeting MSLN (mesothelin) are recruiting patients. Interested patients with mesothelioma and other solid tumors can submit pathological reports, treatment experience and hospitalization summary and other information through the Cancer-Free Home Medical Department for a preliminary evaluation of whether this therapy can be used.
There is a long way to go, and CAR-T therapy will bring new hope to more patients with solid tumors!
recently published an article on the ten-year development and clinical application of CAR-T cell therapy in the internationally renowned journal "Lancet-Hematology". It elaborates that as of November 15, 2021, 714 clinical studies of CAR-T cell therapy have been registered in China, including 510 on ClinicalTrials.gov and 204 on China clinical trial registration studies.
The number of INDs for CAR-T cell therapy in China continues to increase. 73 CAR-T cell products from 32 companies have submitted IND applications, and 36 have received implicit permission to enter clinical trials. Among them, acute lymphoblastic leukemia and non-Hodgkin lymphoma are one of the most common indications.
Among them, the domestically developed of Legend Biotech, Cedagene Biotech , GCC19CART of Stance Biotech, and Claudin18.2 CAR-T of Keji Pharmaceutical have all reached the world's leading level. In addition, many companies are deploying next-generation CAR-T and allogeneic CAR-T technologies. The preliminary data are excellent and they are expected to gain global market share.
In 2021, our country ushered in the first year of cellular immunotherapy. As a pioneer, CAR-T therapy is one of the future development directions. CAR-T therapy mainly focuses on modifying T cells to recognize special targets of tumor cells. In theory, there can be countless kinds of CAR-T therapies targeting different targets, which means there are endless possibilities.
hopes that in the near future, with the efforts of domestic and foreign medical researchers, the toxic and side effects of cell therapy can be reduced, the price can be reduced, the bottleneck of solid tumors can be broken, and more and more patients with advanced cancer can benefit!
This article is original from Cancer Free Home
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