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Construction of chlorogenic acid-containing liposomes with prolonged antitumor immunity based on t cell regulation

Science China(Life Sciences) 2021年第7期64卷 1097-1115页

作者： Yun Zhang Yanfang Yang Jun Ye Yue Gao Hengfeng Liao Junzhuo Zhou Yu Feng Dongdong Liu Yingying Meng Xiaoguang Chen Lili Gao Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

As a potential cancer immunotherapeutic agent,chlorogenic acid(CHA)has entered phase II clinical trials in China as a lyophilized powder formulation for treating ***,the in vivo instability of CHA necessitates daily intramuscular injections,resulting in patient *** this study,CHA-phospholipid complex(PC)-containing PEGylated liposomes(CHA-PC PEG-Lipo,named as CPPL),with CHA-PC as the drug intermediate,were prepared to lower the administration *** demonstrated excellent physicochemical properties,enhanced tumor accumulation,and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes(CHA-PC Lipo,labeled as CPL),both of which only demonstrated antitumor efficacy with once-daily *** evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL,such as stimulating both CD4+and CD8+t cell infiltration,inhibiting myeloid-derived suppressor cell expression,reducing the expression of th2 related factors,and notably,increasing the memory t cells in tumor *** CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via t cells,especially memory t cell regulation.

关键词： chlorogenic acid PEGylated liposomes t cell regulation immunotherapy

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the Qa-1 Dependent CD8^+ t cell Mediated Regulatory Pathway

引用

cellular & Molecular Immunology 2005年第3期2卷 161-167页

作者： Hong Jiang~(1,2) ~1Department of Medicine,Division of Rheumatology,College of Physicians & Surgeons,Columbia University,USA ~2Corresponding to:Dr.Hong Jiang,Department of Medicine,Division of Rheumatology,College of Physicians & Surgeons,Columbia University,630 W.168th Street,PH 8-E Ste.101,New York,NY 10032,USA. Department of Medicine Division of Rheumatology College of Physicians & Surgeons Columbia University New York NY 10032 USA. HJ4@columbia.edu

the immune system has evolved a variety of regulatory mechanisms to ensure the peripheral self-tolerance as well as the optimal capacity to elicit effective anti-infection immunity. At present, there is no satisfactory conceptual framework to explain how the peripheral immunity is regulated at a biological system level, which enables the immune system to perform its essential functions to mount effective immunity to virtually any foreign antigens but avoid harmful immune responses to self. In this regard, during the past few years, an “affinity/avidity model of peripheral t cell regulation” has been proposed and tested, which opens up a new paradigm to understand how the peripheral immunity, to both self and foreign antigens, is regulated. the paradigm is based on the discovery of a subset CD8^＋ t cells with tCRs which specifically recognize a unique set of self-peptides presented by the MHC class Ib molecule Qa-I differentially expressed on t cells as a function of the affinity/avidity of t cell activation. these Qa-1 restricted CD8^＋ t cells represent an example of how the immune system utilizes a unified mechanism to regulate adaptive immunity to both self and foreign antigens. thus, by selectively down-regulating t cells of intermediate affinity/avidity, to any antigens, the immune system controls the adaptive immunity without the necessity to distinguish self from non-self in the periphery at the level of t cell regulation. cellular ＆ Molecular Immunology. 2005;2（3）：161-167.

关键词： t cell regulation CD8^+ t cell affinity/avidity Qa- 1 tCR

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