今天，树木都含苞待放
“看啊，朋友们，春天来了，大地欣然接受了太阳的拥抱，我们很快就会看到它们爱的成果.”
坐牛，亨克帕帕-拉科塔族领袖
“Behold, my friends, the spring is come; the earth has gladly received the embraces of the sun, and we shall soon see the results of their love.”
—Sitting Bull (Tȟatȟáŋka Íyotake), Hunkpapa Lakota Sioux leader (1831-1890)
“看啊，朋友们，春天来了，大地欣然接受了太阳的拥抱，我们很快就会看到它们爱的成果.”
坐牛，亨克帕帕-拉科塔族领袖
“Behold, my friends, the spring is come; the earth has gladly received the embraces of the sun, and we shall soon see the results of their love.”
—Sitting Bull (Tȟatȟáŋka Íyotake), Hunkpapa Lakota Sioux leader (1831-1890)
#百炼成神动画[超话]##百炼成神动画#
She don't want to being Luo Zheng teacher anymore,, it's seems she has falling in love with him [哇][抱一抱][阴险][笑而不语]
But Luo Zheng already has Xiao Die in his heart [笑而不语][笑cry]
Anyway in the end Suliang also as Luo Zheng wife right?
This mc has 3 wife ✌️
She don't want to being Luo Zheng teacher anymore,, it's seems she has falling in love with him [哇][抱一抱][阴险][笑而不语]
But Luo Zheng already has Xiao Die in his heart [笑而不语][笑cry]
Anyway in the end Suliang also as Luo Zheng wife right?
This mc has 3 wife ✌️
Small-molecule-mediated control of the anti-tumour activity and off-tumour toxicity of a supramolecular bispecific T cell engager
#RollingARound##生物医学工程#
https://t.cn/A6YTyJ0g
Background: The broader clinical use of bispecific T cell engagers for inducing anti-tumour toxicity is hindered by their on-target off-tumour toxicity and the associated neurotoxicity and cytokine-release syndrome.
#抗体疗法# These bispecific molecules are created by linking the targeting regions of two antibodies. One arm of the BiTE molecule binds to CD3, an antigen found on the surface of T cells. The other arm is engineered to bind to a tumor-associated antigen (TAA).
When both targets are engaged, the BiTE® molecule forms a bridge between the cytotoxic T cell and the tumor cell, which enables the T cell to recognize the tumor cell and fight it through an infusion of toxic molecules.
When both arms of the BiTE® molecule are bound to their specific targets, a synapse forms between the T cell and the cancer cell. The T cells release perforin to form a pore in the wall of the cancer cells, and toxic molecules called granzymes flow through the pore, leading to the death of the cancer cell.
Q: Mechanism of eliciting off-tumor toxicity?
A: Many tumor-specific antigens are intracellular and are not accessible for standard T-cell engagers, while numerous cell-surface TAAs overexpressed in solid tumors lack high specificity and are often found at low levels in normal tissues. As a consequence, “on-target, off-tumor” toxicity has been a challenge in TAA selection for solid tumors.
Goal: tune down the off-tumour toxicity of bispecific T cells by switchable bispecific T cell nanoengager (SiTE) for controllable cancer immunotherapy
Approach: disengaging the T cells from the tumour cells via the infusion of the small-molecule drug amantadine, which disassembles the supramolecular aggregate
Q: How does the bispecific antibody work? Its efficacy against blood cancer and in solid tumor?
A: One arm of the BiTE molecule binds to CD3, an antigen found on the surface of T cells. The other arm is engineered to bind to a tumor-associated antigen (TAA). The SiTE was prepared using a supramolecular chemistry-based method to assemble the Fab fragments of antibodies targeting both T cells and tumour cells.
CD3 and HER2 Fabs were conjugated to phenyl-modified poly(ethylene glycol) (PEG-phenyl) and β-cyclodextrin (β-CD)-modified PEG (PEG-β-CD). SiTE-induced T cell–cancer cell engagement can be quickly broken with the addition of AMD because of the higher affinity of β-CD and AMD compared with phenyl.
Q: How does amantadine work in this context?
A: SiTE can be disassembled using an infusion of the small molecule amantadine (AMD)—allowing for these toxicities to be halted immediately upon infusion.
E0771–HER2 mouse model with liver expression of human HER2 antigen-High doses of SiTE elicit a tumour-specific immune response with limited on-target off-tumour toxicity
****A potential risk of this SiTE is that it might induce T cell crosslinking and cytokine release because random rather than site-specific conjugation of PEG-phenyl and PEG-β-CD to CD3 and HER2 antibodies were used for all experiments in this work.
#我学#
#RollingARound##生物医学工程#
https://t.cn/A6YTyJ0g
Background: The broader clinical use of bispecific T cell engagers for inducing anti-tumour toxicity is hindered by their on-target off-tumour toxicity and the associated neurotoxicity and cytokine-release syndrome.
#抗体疗法# These bispecific molecules are created by linking the targeting regions of two antibodies. One arm of the BiTE molecule binds to CD3, an antigen found on the surface of T cells. The other arm is engineered to bind to a tumor-associated antigen (TAA).
When both targets are engaged, the BiTE® molecule forms a bridge between the cytotoxic T cell and the tumor cell, which enables the T cell to recognize the tumor cell and fight it through an infusion of toxic molecules.
When both arms of the BiTE® molecule are bound to their specific targets, a synapse forms between the T cell and the cancer cell. The T cells release perforin to form a pore in the wall of the cancer cells, and toxic molecules called granzymes flow through the pore, leading to the death of the cancer cell.
Q: Mechanism of eliciting off-tumor toxicity?
A: Many tumor-specific antigens are intracellular and are not accessible for standard T-cell engagers, while numerous cell-surface TAAs overexpressed in solid tumors lack high specificity and are often found at low levels in normal tissues. As a consequence, “on-target, off-tumor” toxicity has been a challenge in TAA selection for solid tumors.
Goal: tune down the off-tumour toxicity of bispecific T cells by switchable bispecific T cell nanoengager (SiTE) for controllable cancer immunotherapy
Approach: disengaging the T cells from the tumour cells via the infusion of the small-molecule drug amantadine, which disassembles the supramolecular aggregate
Q: How does the bispecific antibody work? Its efficacy against blood cancer and in solid tumor?
A: One arm of the BiTE molecule binds to CD3, an antigen found on the surface of T cells. The other arm is engineered to bind to a tumor-associated antigen (TAA). The SiTE was prepared using a supramolecular chemistry-based method to assemble the Fab fragments of antibodies targeting both T cells and tumour cells.
CD3 and HER2 Fabs were conjugated to phenyl-modified poly(ethylene glycol) (PEG-phenyl) and β-cyclodextrin (β-CD)-modified PEG (PEG-β-CD). SiTE-induced T cell–cancer cell engagement can be quickly broken with the addition of AMD because of the higher affinity of β-CD and AMD compared with phenyl.
Q: How does amantadine work in this context?
A: SiTE can be disassembled using an infusion of the small molecule amantadine (AMD)—allowing for these toxicities to be halted immediately upon infusion.
E0771–HER2 mouse model with liver expression of human HER2 antigen-High doses of SiTE elicit a tumour-specific immune response with limited on-target off-tumour toxicity
****A potential risk of this SiTE is that it might induce T cell crosslinking and cytokine release because random rather than site-specific conjugation of PEG-phenyl and PEG-β-CD to CD3 and HER2 antibodies were used for all experiments in this work.
#我学#
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