This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstr...This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstracts four elements, namely, antigen, antibody, reaction rules among antibodies, and driving algorithm describing how the rules are applied to antibodies, to simulate the process of immune response. Some reaction rules including clonal selection rules, immunological memory rules and immune regulation rules are introduced. Using the theorem of Markov chain, it is proofed that the new model is convergent. The experimental study on the optimal approximation of a stable linear system and an unstable one show that the approximate models searched by the new model have better performance indices than those obtained by some existing algorithms including the differential evolution algorithm and the multi-agent genetic algorithm.展开更多
Adoptive chimeric antigen receptor(CAR)-engineered natural killer(NK)cells have shown promise in treating various cancers.However,limited immunological memory and access to sufficient numbers of allogenic donor cells ...Adoptive chimeric antigen receptor(CAR)-engineered natural killer(NK)cells have shown promise in treating various cancers.However,limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications.Here,we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein(FITC)single-chain variable fragment(scFv)to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors.We next genetically engineer human pluripotent stem cells(hPSCs)with optimized CARs and differentiate them into functional dual CAR-NK cells.The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3(pSTAT3)and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptorβ-chain(ΔIL-2Rβ)and STAT3-binding tyrosine-X-X-glutamine(YXXQ)motif.Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells.Collectively,our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.展开更多
Innate lymphoid cells(ILCs)are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors;however,recent studies have revealed the adaptive features of ILCs.Mouse cytomegalovirus(MCM...Innate lymphoid cells(ILCs)are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors;however,recent studies have revealed the adaptive features of ILCs.Mouse cytomegalovirus(MCMV)-and cytokine-induced memory natural killer(NK)cells circulate in the blood and are referred to as conventional memory NK cells.In contrast,virusand hapten-induced memory NK cells,hapten-induced memory ILC1s,and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung,and are referred to as tissue-resident memory ILCs.Considering their similar migration patterns and memory potential,tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T(T r m)cells.Both tissue-resident memory ILCs and TRM cells share common characteristics in terms of dynamics,phenotype,and molecular regulation.The emergence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression.This review discusses the evidence supporting tissue-resident memory NK cells and other memory ILC subsets,compares them with TRM cells,and highlights key unsolved questions in this emerging field.展开更多
Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are cur...Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance ofHBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.展开更多
The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade(ICB)therapy in solid tumors.It is important and imperative to search new strategies to relieve tumor hypoxi...The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade(ICB)therapy in solid tumors.It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors.In this study,the oxygen(O_(2))self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors.The nanoplatform can produce O_(2)by catalyzing hydrogen peroxide(H_(2)O_(2))in tumor site effectively,showing excellent photodynamic therapy(PDT)performance.Meanwhile,it can further trigger immunogenic cell death(ICD),enhance T cell infiltration,reverse immunosuppression,and reprogram the immune-cold tumor microenvironment.In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect.The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos,60133010 and 60372045)the Graduate Innovation Fund of Xidian University(Grant No.05004),
文摘This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstracts four elements, namely, antigen, antibody, reaction rules among antibodies, and driving algorithm describing how the rules are applied to antibodies, to simulate the process of immune response. Some reaction rules including clonal selection rules, immunological memory rules and immune regulation rules are introduced. Using the theorem of Markov chain, it is proofed that the new model is convergent. The experimental study on the optimal approximation of a stable linear system and an unstable one show that the approximate models searched by the new model have better performance indices than those obtained by some existing algorithms including the differential evolution algorithm and the multi-agent genetic algorithm.
基金supported by startup funding from the Davidson School of Chemical Engineering and the College of Engineering at Purdue(X.B.)PICR Robbers New Investigators(X.B.),Showalter Research Trust(Young Investigator Award to X.B.)+2 种基金NSF CBET(grant no.2143064 to X.B.)NSF CBET(grant no.1943696 to X.L.L.)NIH NCI(grant no.R37CA265926 to X.B.).
文摘Adoptive chimeric antigen receptor(CAR)-engineered natural killer(NK)cells have shown promise in treating various cancers.However,limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications.Here,we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein(FITC)single-chain variable fragment(scFv)to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors.We next genetically engineer human pluripotent stem cells(hPSCs)with optimized CARs and differentiate them into functional dual CAR-NK cells.The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3(pSTAT3)and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptorβ-chain(ΔIL-2Rβ)and STAT3-binding tyrosine-X-X-glutamine(YXXQ)motif.Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells.Collectively,our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.
基金supported by the National Natural Science Foundation of China(Grant Nos.81788101,81761128013 and 91542000)Anhui Provincial Natural Science Foundation(1908085MC65).
文摘Innate lymphoid cells(ILCs)are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors;however,recent studies have revealed the adaptive features of ILCs.Mouse cytomegalovirus(MCMV)-and cytokine-induced memory natural killer(NK)cells circulate in the blood and are referred to as conventional memory NK cells.In contrast,virusand hapten-induced memory NK cells,hapten-induced memory ILC1s,and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung,and are referred to as tissue-resident memory ILCs.Considering their similar migration patterns and memory potential,tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T(T r m)cells.Both tissue-resident memory ILCs and TRM cells share common characteristics in terms of dynamics,phenotype,and molecular regulation.The emergence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression.This review discusses the evidence supporting tissue-resident memory NK cells and other memory ILC subsets,compares them with TRM cells,and highlights key unsolved questions in this emerging field.
文摘Prevention of hepatitis B virus(HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance ofHBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.
基金This work is supported by the National Natural Science Foundation of China(Nos.52103164,and 52173142)Guangdong Basic and Applied Basic Research Foundation(Nos.2021A1515220033 and 2020A1515111059)the Fundamental Research Funds for the Central Universities(No.JUSRP123079).
文摘The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade(ICB)therapy in solid tumors.It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors.In this study,the oxygen(O_(2))self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors.The nanoplatform can produce O_(2)by catalyzing hydrogen peroxide(H_(2)O_(2))in tumor site effectively,showing excellent photodynamic therapy(PDT)performance.Meanwhile,it can further trigger immunogenic cell death(ICD),enhance T cell infiltration,reverse immunosuppression,and reprogram the immune-cold tumor microenvironment.In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect.The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.
