In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles intr...In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.展开更多
Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoin...Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoint therapy has attracted considerable attention.The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation.But antibodies-based immunotherapy confronted with some disadvantages,such as immunogenicity,stability,membrane permeability,and production cost.Therefore,alternative approaches including small-molecule-regulated immune response are being introduced.In this review,we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive,which highlights the great potential of natural products in this field.展开更多
We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells...We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells: killer T (TK), natural killer (NK), lymphokine activated killer (LAK) cells. Both TX and TO inhibited the growth of tumors that express estrogen receptors. Thus these antiestrogens inhibited tumor growth and stimulated killer cells for cytotoxicty on such tumors. Therefore these agents were presumed to stimulate tumor immunity. We tested the P815 mouse mastcytoma with TK, LK, and TX or TO. A therapeutic effect was observed in both experiments. The SL2-5 murine lymphoma was tested with NK and TX cells or TO cells and successful immunotherapy was observed.?We digested human breast carcinomas and lung tumors with collagenase. The killer cells were separated from tumor cells on Ficoll gradients. TX and TO enhanced the cytotoxic effect of autologous killer cells on the corresponding tumor cells. This experiment indicates that the results obtained in animals are also valid for human malignant disease.展开更多
Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or a...Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.展开更多
Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and com...Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.展开更多
The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand(4-1BBL)plays an important role in the activation,proliferation and differentiation of T lymphocytes.The function of 4-1BB/4-1BBL expressed by the immu...The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand(4-1BBL)plays an important role in the activation,proliferation and differentiation of T lymphocytes.The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts.In this study,4-1BBL was expressed in non-immune cells and non-tumor cells,and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated.The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed,and the plasmid was transfected into baby hamster kidney(BHK)cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly.The study demonstrated that the molecule 4-1BBL expressed by BHK cells in vitro could enhance the proliferation and cytotoxicity of lymphocytes,and it could increase the expression level of IL-2 and IFN-γ.The treatment with plasmid p4-1BBL in vivo revealed that the number of CD8+Tcells in the peri-tumoral tissue increased markedly,and the growth rate of the tumor was significantly lower than that of control group.Thesefindings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes.This therapeutic method may provide a promising approach for tumor immunotherapy.展开更多
文摘In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.
基金supported financially by the funding of Exploitation and Utilization of Abundant Natural Products from Plants from Kunming Institute of Botany(KIB2017009)the National Natural Science Foundation of China(U1402227)+2 种基金the 100 Talents Program of the Chinese Academy of Sciences(Y.Li)the Program of Recruited Top Talent of Sciences and Technology of Yunnan Province(2009CI120)the Independent Program of Key Laboratory of Natural Pharmaceutical Chemistry of Yunnan Province(Y.Li).
文摘Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoint therapy has attracted considerable attention.The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation.But antibodies-based immunotherapy confronted with some disadvantages,such as immunogenicity,stability,membrane permeability,and production cost.Therefore,alternative approaches including small-molecule-regulated immune response are being introduced.In this review,we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive,which highlights the great potential of natural products in this field.
文摘We examined the possibility that the anti-estrogens, tamoxifen (TX) and toremifen (TO) interacted?with the immune system. Indeed, both TX and TO stimulated cells mediated cytotoxicity reactions by various killer cells: killer T (TK), natural killer (NK), lymphokine activated killer (LAK) cells. Both TX and TO inhibited the growth of tumors that express estrogen receptors. Thus these antiestrogens inhibited tumor growth and stimulated killer cells for cytotoxicty on such tumors. Therefore these agents were presumed to stimulate tumor immunity. We tested the P815 mouse mastcytoma with TK, LK, and TX or TO. A therapeutic effect was observed in both experiments. The SL2-5 murine lymphoma was tested with NK and TX cells or TO cells and successful immunotherapy was observed.?We digested human breast carcinomas and lung tumors with collagenase. The killer cells were separated from tumor cells on Ficoll gradients. TX and TO enhanced the cytotoxic effect of autologous killer cells on the corresponding tumor cells. This experiment indicates that the results obtained in animals are also valid for human malignant disease.
基金This work was partly supported by NCI grant R01CA229818 to Garcia-Sastre A.
文摘Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.
文摘Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.
基金supported in part by the National Natural Science Foundation of China(No.30600735)the Special Funds for Major State Basic Research Program of China(973 Program)(No.2002CB513100).
文摘The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand(4-1BBL)plays an important role in the activation,proliferation and differentiation of T lymphocytes.The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts.In this study,4-1BBL was expressed in non-immune cells and non-tumor cells,and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated.The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed,and the plasmid was transfected into baby hamster kidney(BHK)cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly.The study demonstrated that the molecule 4-1BBL expressed by BHK cells in vitro could enhance the proliferation and cytotoxicity of lymphocytes,and it could increase the expression level of IL-2 and IFN-γ.The treatment with plasmid p4-1BBL in vivo revealed that the number of CD8+Tcells in the peri-tumoral tissue increased markedly,and the growth rate of the tumor was significantly lower than that of control group.Thesefindings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes.This therapeutic method may provide a promising approach for tumor immunotherapy.
