The latest research progress of car-t cell therapy (phase 11)

December 31, 2019 / BIOON / -- car-t (chimeric antigen receptor T-cell immunotherapy), i.e chimeric antigen receptor T-cell immunotherapy It is a new cell therapy which has been used in clinic for many years It has a significant effect on the treatment of acute leukemia and non-Hodgkin's lymphoma, and is considered to be one of the most promising tumor treatment methods Just like all technologies, car-t technology has also experienced a long evolution process It is in this series of evolution process that car-t technology gradually matures The key point of this new treatment strategy is to recognize the artificial receptor called chimeric antigen receptor (car) of the target cell, and after gene modification, the patient's T cell can express the car In human clinical trials, scientists extract some T cells from the diseased human body through a process similar to dialysis, and then genetically modify them in the laboratory to import the gene encoding the car, so that these T cells can express the new receptor These genetically modified T cells proliferate in the laboratory and are then infused back into the diseased body These T cells use their expressed car receptors to bind to molecules on the surface of the target cells, and this binding triggers an internal signal generation, which then activates these T cells so effectively that they quickly destroy the target cells In recent years, car-t immunotherapy is not only used to treat acute leukemia and non Hodgkin's lymphoma, but also used to treat solid tumor, autoimmune disease, HIV infection and heart disease and other diseases after improvement Based on this, in view of the latest progress of car-t cell therapy, this article makes an inventory for readers 1 Cell: human glioblastoma like organs can reproduce tumor characteristics, and can be used to evaluate the efficacy of drugs and car-t cells doi: 10.1016/j.cell.2019.11.036 glioblastoma is the most aggressive and common form of brain cancer The laboratory brain like organ, which is developed from a patient's own glioblastoma, may provide the answer to how best to treat it In a new study, researchers from the University of Pennsylvania found that glioblastoma like organs may be an effective model to quickly test personalized treatment strategies The relevant research results were published online in the cell Journal on December 26, 2019, with the title of "genetic relationships, new loci, and pleiotopic mechanisms across eight psychological disorders" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.11.036 In the new study, the researchers took fresh tumor samples from 52 patients in order to "grow" tumor like organs in the laboratory Within two weeks, the total success rate of producing glioblastoma like organs was 91.4%, among which 66.7% of tumors showed IDH1 mutation, 75% of recurrent tumors showed IDH1 mutation These glioblastoma like organs can also be stored in a biobank for later analysis The researchers also performed genetic, histological, and molecular analyses in 12 patients to determine that these new glioblastoma like organs largely retain the characteristics of the patient's primary tumor They successfully transplanted eight samples of glioblastoma like organs into the brains of adult mice Their brains showed rapid invasive infiltration of cancer cells and maintained the expression of key mutated genes three months later Importantly, a major feature of glioblastoma, tumor cells infiltrating into the surrounding brain tissue, was observed in the mouse model In order to simulate the post-operative treatment, the researchers conducted standard and targeted treatment for glioblastoma like organs, including drugs from clinical trials and car-t immunotherapy For each treatment, they found that the response of these organs to treatment was different, and the effectiveness of treatment was related to gene mutations in patients' tumors This model provides the possibility for future clinical trials based on the individual treatment of different drug reactions of patients' tumors 2 Clinical research shows that car-t cell therapy can effectively treat recurrent mantle cell lymphoma news source: Car T cell therapy effective for relapsed mantle cell lymphama patients Patients with lymphama may benefit from car-t therapy targeting CD19 The results were presented at the 61st annual meeting and exhibition of the American Society of Hematology in Orlando, Florida on December 9, 2019 The multicenter phase II clinical study, called zuma-2, reported that 93% of patients responded to the car-t cell therapy, and 67% of them achieved complete response Of the top 28 patients treated, 43% remained in remission after two years This study reported grade 3 side effects, the most common being anemia and thrombocytopenia Most patients have experienced cytokine release syndrome, which is a common side effect of car-t cell therapy, but this syndrome is effectively controlled in all patients 3 Nature subjournal: powerful! A thin metal membrane can efficiently deliver car-t cells to solid tumors doi: 10.1038/s41551-019-0486-0 in a new study, researchers from the Fred Hutchinson Cancer Research Center in the United States found for the first time that a small and thin metal mesh loaded with anti-cancer immune cells can shrink tumors in a preclinical model of ovarian cancer The related research results were recently published in the Journal of natural biomedical engineering The title of the paper is "nitinol thin films functionalized with car-t cells for the treatment of solid tumours" The picture is from Fred Hutchinson Cancer Research Center Dr Matthias Stephan, co-author of the paper and researcher of the Fred Hutchinson Cancer Research Center, said, "cell therapy against cancer has been a great success in blood cancer, but not in solid tumors Our findings suggest that thin metal mesh loaded with genetically engineered T cells to fight ovarian cancer can clear 70% of treated mice of tumors, which makes us an important step towards the goal of effective cytotherapy against solid tumors " 4 Nature: breakthrough! Scientists have successfully reprogrammed T cells to improve the effectiveness of cancer immunotherapy! Doi: 10.1038/s41586-019-1821-z recently, in a research report published in the international journal Nature, scientists from St Jude Children's research hospital and other institutions developed a new treatment strategy to effectively enhance cancer immunotherapy, which may effectively slow down the growth of tumor and prolong the life span of cancer bearing mice This study may provide a promising strategy for the development of more effective adoptive cell therapy, such as car T cell therapy: immunotherapy aims to use tumor specific T cells of patients' body to treat cancer Before these T cells are re input into patients' body, researchers will collect and expand their functions After re input into patients, some patients will respond significantly to the therapy, while adoptive cell therapy may not be effective Resist solid tumors In this paper, the researchers use crispr-cas9 technology to identify a special enzyme molecule in tumor specific T cells, which is similar to the "brake", which can shut down the anti-tumor immune response of the body When the enzyme molecule named reverse-1 is removed, the T cells will become long-lived, and the efficacy and accumulation in the tumor will increase When the lack of reg is used, the T cells will become long-lived When nase-1 T cells were used to treat mice with leukemia and melanoma, the life span of the mice was prolonged, and the tumor size in these mice was also reduced compared with the mice treated with conventional T cells (wild type) Researcher Jun Wei said that previous researchers have found that regenase-1 can limit the activation of T cells In this study, we found that regenase-1 can also inhibit two important T cell signaling pathways After screening with crispr-cas9, researchers found that the transcription factors BATF and Tcf-1 may be the targets of regenase-1 The researchers pointed out that BATF can drive the metabolism of T cells to enhance t-fine The accumulation of cells and the ability to kill tumor cells, while Tcf-1 can promote the longevity of T cells, the traditional view is that the above process is interactive, increasing the anti-tumor activity of T cells means that T cells become longer, but the results of this study found that in fact, it may not be so According to the researchers, combination therapy may be the key to the clinical success of cancer immunotherapy For this reason, the researchers also want to provide more insights on the clinical potential of the research findings After the second crispr-cas9 screening, the researchers identified two more relevant molecules When these molecules (signal factors PTPN2 and SOCS1) were removed together with the regenase-1 The expression of T cells in cancer immunotherapy will be significantly improved in mice PTPN2 and SOCS1 may not depend on the function of regenase-1 Later researchers will conduct more in-depth research to clarify how to develop new anti-cancer therapy through the targeted effect of regenase-1 5 Nature: scientists have developed a new generation of car-t cells resistant to "fatigue" state to successfully resist solid tumor doi: 10.1038/s41586-019-1805-z Recently, in a research report published in the international journal Nature, scientists from Stanford University Medical Center have developed a new method through research, which may reprogram car-t cells (immune cells against cancer) to extend their own activity and increase the potential of human cancer cells in defense laboratory culture and mouse body Photo source: cc0 public domain In 2017, car-t cells became the star cells of global concern After that, FDA approved them for the treatment of relapsed or unresponsive acute lymphoblastic leukemia Later in the same year, another version of car-t cell therapy was also approved for the treatment of some types of lymphoma Although the response of blood cancer to car-t cell therapy is better, less than half of patients need to control their disease for a long time, usually because car-t cells are "tired", they lose the ability to constantly proliferate and resist cancer cells, overcome this "tired" state or the purpose of many years of cancer researchers to carry out a lot of research In this study, the researchers analyzed what happens when T cells are "tired" and whether they are likely to effectively inhibit the "tired" of such cells; using a new technology called ATAC SEQ, the researchers were able to identify the genomic regions of genes that are overexpressed or underexpressed in regulatory circuits When we used this technique to compare the genomes of healthy and "tired" T cells, we identified some significant differences in gene expression patterns, especially when we found that "tired" T cells exhibit a wide range of bases