Latest Research Advances in CAR-T Cell Therapy (No. 19)

January 31, 2021 // ---CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy), a chimeric antigen receptor T-cell immunotherapy.
therapy is a new type of cell therapy that has been available for many years but has only been improved in recent years to be used in clinical practice.
is considered one of the most promising treatments for acute leukemia and non-Hodgkin's lymphoma.
as with all technologies, CAR-T technology has gone through a long evolutionary process, and it is in this series of evolutions that CAR-T technology has matured.
key to this new treatment strategy is to identify artificial receptors called chimeric antigen receptors (CAR) in the target cells, and after genetic modification, the patient's T cells are able to express the CAR.
In human clinical trials, scientists extracted some T-cells from patients through a dialysis-like process, then genetically modified them in the laboratory to import the genes that encode the CAR so that the T-cells could express the new subject.
these genetically modified T-cells are proliferated in the lab and then perfused back into the patient.
These T-cells use the CAR subjects they express to bind to molecules on the surface of the target cell, which triggers the production of an internal signal that then activates the T-cells so powerfully that they quickly destroy the target cells.
in recent years, CAR-T immunotherapy has been used to treat diseases such as solid tumors, autoimmune diseases, HIV infections and heart disease, in addition to acute leukemia and non-Hodgkin's lymphoma.
based on this, the editor-in-chief has made an inventory of the latest advances in CAR-T cell therapy to reach out to readers.
1.Nat Commun: SynNotch CAR-T cells targeting GD2 and B7H3 are expected to treat neuroblastoma doi:10.1038/s41467-020-20785-x-inlay antigen-inset antigen (CAR) T-cell (CAR-T) therapy has revolutionized the treatment of leukemia.
, the treatment is not effective in treating solid tumors, including childhood cancers such as neuroblastoma.
preclinical study of neuroblastoma using certain CAR-T cells revealed toxic effects.
build highly specific and efficient GD2-B7H3 T cells, pictured from Nature Communications, 2021, doi:10.1038/s41467-020-20785-x.
Now, in a new study, researchers at Children's Hospital Los Angeles have developed an improved version of car-T cells that show hope in targeting neuroblastoma: killing cancer cells more effectively without harming healthy brain tissue.
the study is still in its preclinical stage, it reveals the potential for life-saving treatments for children and adults with solid tumors.
study was published in the journal Nature Communications on 21 January 2021 under the title "Preclinical assessment of of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T metastatic neuroblastoma".
2.Hepatology: New study shows IDRA HBV-TCR-T cells attack hepatocellular carcinoma while temporarily immune from immunosuppressive drugs doi:10.1002/hep.31662 in In a new study, researchers from Duke-Singapore National University School of Medicine and other research institutions in Singapore designed an armed immune cell that can attack relapsed cancer in liver transplant patients while temporarily avoiding immunosuppressants taken by patients to avoid organ rejection.
study, published recently in the journal Hepatology, was titled "Immunosuppressive Drug Resistant Armored TCR T cells for immune-therapy of HCC in liverist patients". Co-author of the
paper, Professor Antonio Bertoletti, of Duke-Singapore National University School of Medicine, said: "We have developed a way to make T cells specifically targeting HBV antigens in liver cancer cells, while making them resistant to two commonly used immunosuppressants--- tacrolimus and mycophenolate ---.
, Professor Bertoletti added, "It is important that our T-cell resistance to immunosuppressants lasts only about four days, after which they regain sensitivity to these drugs."
"3. Nature sub-journal paper detailed! CAR-T cells targeting CXCR5 are expected to treat fenticular lymphoma and chronic lymphocytic leukemia doi:10.1038/s41467-020-20488-3 In a new study, researchers from Max Delbrook Molecular Medical Center in Germany developed a new CAR-T cell therapy.
found this approach to be very effective, especially in the fight against figular lymphoma and chronic lymphocytic leukemia (CLL).
results were published in the journal Nature Communications on 11 January 2021 under the title "CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's mphlyoma and tumor-support follicular T helper cells".
images from Nature Communications, 2021, doi:1038/s41467-020-20488-3.
's defenses don't usually recognize cancer cells as dangerous cells.
In order to correct this sometimes fatal error, the researchers are working on a clever new idea that involves extracting small amounts of immune cells from cancer patients and "reinventing" them in the lab so that they can identify certain surface proteins in malignant tumor cells.
then, they multiply these immune cells and inject them back into the blood of the same patient --- and let them begin to travel through the body, detecting and attacking all cancer cells in a targeted manner.
4. Heavy! Scientists have identified new targets that could help develop safe and effective CAR-T cell therapies for pancreatic cancer! doi:10.1158/1078-0432.CCR-19-2163 Recently, an article published in the international magazine Clinical Cancer Research entitled "CEACAM7 Is Effective Target for CAR T-Cellrapy of Pancreatic Ductal Aden" In the study, scientists from the University of London and others found a specific protein that could be used as a potential therapeutic target for the development of new treatments for pancreatic cancer, using the protein as a target to successfully develop a CAR-T cell therapy (a class of immunotherapy) to kill pancreatic cancer cells in preclinical models.
using a special technique called immunostaining, the researchers analyzed the presence of CEACAM7 in human PDAC samples and normal tissues and found that a large proportion of the PDAC samples tested were able to express CEACAM. 7 molecule, but the protein does not exist in some normal tissues, including tonsils, lung tissue, liver and prostate, suggesting that CEACAM7 may be an ideal target to help develop CAR-T cell therapy for pancreatic cancer.
To determine the potential of CEACAM7 as a therapeutic target, the researchers developed a CAR-T cell that can target CEACAM7 molecules and apply it to PDAC cell line and PDAC preclinical models, where CAR-T cells can effectively target cells that act on the CEACAM7 molecule and eliminate cancer cells in late-stage PDAC preclinical models.
5.Sci Trans Med: The new switch regulates CAR-T cell activity doi:10.1126/scitranslmed.abb6295CAR T cells are an effective cell-based immunotherapy that has been a great success in treating certain advanced cancers, but poses a significant risk of toxic side effects.
, scientists at the Dana-Farber Cancer Institute and Massachusetts Cancer General Hospital created a molecular "ON-OFF" switch to regulate the activity of CAR T cells.
CAR-T cells are immuno-modified immune cells that identify and attack tumor cells.
once given, these "living drugs" multiply and kill tumor cells within weeks to months.
, however, can cause life-threatening inflammatory reactions that are difficult to control.
scientists report in the journal Science Translational Medicine on the development of switchable CAR T cells that can be turned on or off by giving commonly used cancer drugs.
in the lab, the researchers were able to quickly and reversiblely shut it down by using the drug, and then CAR T cells resumed their anti-tumor activity.
, switchable cell therapy may allow patients to adjust their daily CAR T cell activity, which is expected to reduce toxic side effects.
6.JEM: New combination strategies or promising to enhance the effectiveness of breast cancer immunotherapy! Doi:10.1084/jem.20200844 In a recent study published in the international journal Journal of Experiment Medicine, scientists from institutions such as the University of North Carolina found that activating the most famous immune signaling path paths that fight viral and bacterial infections may enhance the ability of genetically engineered T cells to remove breast cancer.
that CAR-T cells that can be used to treat specific types of cancer in humans, when combined with other immunotherapy, can also be effective in treating solid tumors. In the
study, researcher Serody and colleagues tested a variety of strategies in breast cancer mouse models to enhance the effectiveness of CAR-T cells, one of which was to use drugs such as cGAMP to treat mice that were able to activate STING paths in their bodies, an immune cell signaling pathline that normally induces inflammation of the body to respond to invading viruses or bacteria.
Activated STING pathlines can create an inflammatory environment in mouse tumors and improve the ability of CAR-T cells to accumulate and attack tumor cells, which increase when the car-T cells that produce immune signal molecule IL-17A are infused into the mouse body compared to CAR-T cells produced using standard techniques. 'We determined from our study that if therapeutic antibodies were used to treat mice, the attack of CAR-T cells in the body could last longer, and that the therapeutic antibody could remove immunosuppressive cells from the tumor environment and prevent immune checkpoints from insanity of CAR-T cells,' the
researchers said.
researchers found that when all methods were combined, tumors in the body's breasts in mice could be completely eliminated.
7.CRISPR-Cas9 Technology Editor's CAR-T Cells or potential to enhance the body's resistance to blood cancer Source: CRISPR-edited CAR T cells enhanced fight against blood cancers<!--/ewebeditor:page-><!--ewebeditor:page title=" > Recently, at the 62nd Annual Meeting of the American Society of Hematology (ASH) in 2020, scientists from the University of Pennsylvania presented their latest preclinical findings, which found that USing CRISPR/Cas9 technology to remove specific proteins on CAR-T cells that inhibit T-cell activation or enhance the ability of engineered T-cells to remove blood cancers.
researchers removed the gene called CD5 from car-T cells and then infused it back into mice carrying T-cells and B-cell leukemia/lymphoma, which encodes the CD5 protein on the surface of the T-cell and inhibits its activation.
Compared to mice infused with non-edited CAR-T cells, mice with CD5 rejected CAR-T cells had higher levels of T-cell proliferation in in vitro blood, and tumor size decreased significantly, and mice had better survival outcomes.
CRISPR technology could help scientists lock in and compile it