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Recent popular reports from Yimaike ★August·ShanghaiOncolytic virus drug development forum is about to open ★Half-year financing has reached hundreds of millions, and the oncolytic virus has entered the fast laneYimai New Observation Click on the picture and register now June 14, 2021/ EMedClub News/--Tumor microenvironment (TME) is one of the main obstacles faced by CAR-T cell therapy in the treatment of solid tumors
.
TME is the "soil" that tumors rely on for survival.
The immunosuppressive environment in tumors composed of malignant cells, immune components, blood vessels, extracellular matrix and signal molecules affects the body's sensitivity to immunotherapy
.
The research team of Peter McCallum Cancer Center is based on CRISPR/Cas9 gene editing technology to make CAR-T cell therapy more effective against solid cancer
.
Related research results were published in Nature Communications recently
.
Adenosine is one of the key factors that produce immunosuppression in the tumor microenvironment
.
The activation of adenosine A2AR receptors suppresses multiple immune subgroups including T cells, thereby limiting the anti-tumor immune response
.
At present, many pharmaceutical giants are actively deploying drugs for the adenosine pathway
.
Researchers at the Peter McCallum Cancer Center used CRISPR/Cas9 to knock out the A2AR gene in CAR-T cells, and conducted experiments in mice; the results showed that knocking out this gene can significantly improve the efficacy of CAR-T and increase small The number of mouse CAR-T effector cells (Figure C below) and prolong the survival time of mice (Figure B below)
.
▲ Picture source: Nature Communications.
In addition, studies have also shown that the CRISPR/Cas9 knockout strategy of target genes may be more effective than shRNA knockdown or pharmacological blockade (Figure I below), which may be related to the effect of A2AR on adenosine The high affinity is related, which means that any residual A2AR receptor expression can still exert an effective immunosuppressive effect
.
▲ Picture source: Nature Communications Generally speaking, the study shows that using CRISPR/Cas9 to knock out the A2AR gene of CAR-T cells is a superior therapy to enhance the function of CAR-T therapy and can be applied to a variety of adenosines.
Treatment of signal-related tumor types, including breast cancer, ovarian cancer, lung cancer, acute myeloid leukemia, multiple myeloma, and non-Hodgkin’s lymphoma
.
This method has great potential for clinical transformation
.
Many studies have shown that CRISPR/Cas9-mediated deletion of various inhibitory genes (including PD-1, TGFβR and PTPN2) has been proven effective in many types of tumor models; and gene editing PD-1 T cells The therapy has now entered the stage of clinical trials
.
Gene editing technology can achieve targeted insertion of exogenous genes or targeted knockout of endogenous genes, improve the activity and proliferation capacity of immune cells, and thereby improve the effectiveness and safety of immune cell therapy
.
In terms of clinical application, a number of trials on gene editing T cell therapy have been carried out at home and abroad, and the preliminary data obtained proves the optimistic prospects of this technology
.
For more details, click on the QR code to read the reference materials in full: 1.
https:// Yimike is always committed to cutting-edge technology and industry trends in bio-innovative drugs , Industry Insights and other original news reports, all media high-end matrix users reached 160,000+, of which industrial users accounted for more than 50%, scientific research and clinical users accounted for about 30%, and investment institutions users exceeded 5%.
.
In order to promote interactive exchanges in industry segments, we have established a number of professional WeChat groups, welcome to scan the QR code to add groups
.
.
TME is the "soil" that tumors rely on for survival.
The immunosuppressive environment in tumors composed of malignant cells, immune components, blood vessels, extracellular matrix and signal molecules affects the body's sensitivity to immunotherapy
.
The research team of Peter McCallum Cancer Center is based on CRISPR/Cas9 gene editing technology to make CAR-T cell therapy more effective against solid cancer
.
Related research results were published in Nature Communications recently
.
Adenosine is one of the key factors that produce immunosuppression in the tumor microenvironment
.
The activation of adenosine A2AR receptors suppresses multiple immune subgroups including T cells, thereby limiting the anti-tumor immune response
.
At present, many pharmaceutical giants are actively deploying drugs for the adenosine pathway
.
Researchers at the Peter McCallum Cancer Center used CRISPR/Cas9 to knock out the A2AR gene in CAR-T cells, and conducted experiments in mice; the results showed that knocking out this gene can significantly improve the efficacy of CAR-T and increase small The number of mouse CAR-T effector cells (Figure C below) and prolong the survival time of mice (Figure B below)
.
▲ Picture source: Nature Communications.
In addition, studies have also shown that the CRISPR/Cas9 knockout strategy of target genes may be more effective than shRNA knockdown or pharmacological blockade (Figure I below), which may be related to the effect of A2AR on adenosine The high affinity is related, which means that any residual A2AR receptor expression can still exert an effective immunosuppressive effect
.
▲ Picture source: Nature Communications Generally speaking, the study shows that using CRISPR/Cas9 to knock out the A2AR gene of CAR-T cells is a superior therapy to enhance the function of CAR-T therapy and can be applied to a variety of adenosines.
Treatment of signal-related tumor types, including breast cancer, ovarian cancer, lung cancer, acute myeloid leukemia, multiple myeloma, and non-Hodgkin’s lymphoma
.
This method has great potential for clinical transformation
.
Many studies have shown that CRISPR/Cas9-mediated deletion of various inhibitory genes (including PD-1, TGFβR and PTPN2) has been proven effective in many types of tumor models; and gene editing PD-1 T cells The therapy has now entered the stage of clinical trials
.
Gene editing technology can achieve targeted insertion of exogenous genes or targeted knockout of endogenous genes, improve the activity and proliferation capacity of immune cells, and thereby improve the effectiveness and safety of immune cell therapy
.
In terms of clinical application, a number of trials on gene editing T cell therapy have been carried out at home and abroad, and the preliminary data obtained proves the optimistic prospects of this technology
.
For more details, click on the QR code to read the reference materials in full: 1.
https:// Yimike is always committed to cutting-edge technology and industry trends in bio-innovative drugs , Industry Insights and other original news reports, all media high-end matrix users reached 160,000+, of which industrial users accounted for more than 50%, scientific research and clinical users accounted for about 30%, and investment institutions users exceeded 5%.
.
In order to promote interactive exchanges in industry segments, we have established a number of professional WeChat groups, welcome to scan the QR code to add groups
.
