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Abstract:
Immunotherapy products, represented by chimeric antigen receptor-modified T lymphocytes (CAR-T cells), have achieved significant progress in hematologic malignancies such as leukemia. The raw materials used in the production of cell therapy products are diverse and complex, with gene modification vectors and other raw materials that endow cells with specific functionalities or influence their qualities usually classified as crucial raw materials. These crucial raw materials often have significant impacts on the quality attributes and in vivo efficacy of cell therapy products, making them important concerns in the evaluation of cell therapy products. This article summarizes several crucial raw materials that are commonly used in cell therapy products (including lentiviral vectors and γ-retroviral vectors, CRISPR/Cas gene editing system, transposon system, immunomagnetic separation beads, and feeder layer cells) and proposes the current evaluation considerations and risk control strategies with the aim of advancing the clinical transformation and application of such products.
Immunotherapy products, represented by chimeric antigen receptor-modified T lymphocytes (CAR-T cells), have achieved significant progress in hematologic malignancies such as leukemia. The raw materials used in the production of cell therapy products are diverse and complex, with gene modification vectors and other raw materials that endow cells with specific functionalities or influence their qualities usually classified as crucial raw materials. These crucial raw materials often have significant impacts on the quality attributes and in vivo efficacy of cell therapy products, making them important concerns in the evaluation of cell therapy products. This article summarizes several crucial raw materials that are commonly used in cell therapy products (including lentiviral vectors and γ-retroviral vectors, CRISPR/Cas gene editing system, transposon system, immunomagnetic separation beads, and feeder layer cells) and proposes the current evaluation considerations and risk control strategies with the aim of advancing the clinical transformation and application of such products.
Abstract:
Objective: To explore the effects of induced IL-7 expression on proliferation and in vitro antitumor activities of glypican-3 (GPC3)- specific chimeric antigen receptor gene modified-T (CAR-T) cells. Methods: The GPC3 CAR sequence fragment was inserted into the BamHⅠ/EcoRⅠs ite of the GV400 vector using seamless cloning, constructing second-generation CAR lentiviral vectors GPC3-BBZ and GPC3-BBZ-NFAT-IL-7. The lentiviruses were packaged with 293T cells and transfected into healthy human T cells to prepare CAR-T cells， which were divided into non-transduced T cell (NT) group, GPC3-BBZ CAR-T cell group and GPC3-BBZ-NFAT-IL-7 CAR-T cell group. The expression of CAR in CAR-T cells of each group was determined by flow cytometry. IL-7 mRNA expression level in CAR-T cells activated by GPC3 protein was determined by qPCR. The proliferation ability of CAR-T cells under GPC3 antigen stimulation was evaluated by cell counting. The secretion levels of IL-7, IFN-γ, and TNF-α by CAR-T cells after stimulation with tumor cells was determined using ELISA. The cytotoxicity of CAR-T cells against human hepatocellular carcinoma Huh-7 cells was tested by real-time cell analyzer (RTCA). Results: Lentiviral vectors GPC3-BBZ and GPC3-BBZ-NFAT-IL-7 were successfully constructed, and GPC3-specific CAR-T cells were prepared. After activation with GPC3 antigen, GPC3-BBZ-NFAT-IL-7 CAR-T cells effectively expressed IL-7 mRNA (P < 0.01) and exhibited stronger proliferation capacity (P < 0.05). Compared with GPC3-BBZ CAR-T cells, GPC3-BBZ-NFAT-IL-7 CAR-T cells co-cultured with GPC3-positive Huh-7 cells secreted higher levels of IL-7, IFN-γ, and TNF-α (P < 0.01 or P < 0.001). The RTCA results showed that the cytotoxicity of GPC3-BBZ-NFAT-IL-7 CAR-T cells against GPC3-positive Huh-7 cells was significantly higher than that of GPC3-BBZ CAR-T cells (P < 0.05). Conclusion: GPC3-specific CAR-T cells with inducible IL-7 expression were successfully prepared, which exhibited immune activity and tumor cell killing capacity in vitro.
Objective: To explore the effects of induced IL-7 expression on proliferation and in vitro antitumor activities of glypican-3 (GPC3)- specific chimeric antigen receptor gene modified-T (CAR-T) cells. Methods: The GPC3 CAR sequence fragment was inserted into the BamHⅠ/EcoRⅠs ite of the GV400 vector using seamless cloning, constructing second-generation CAR lentiviral vectors GPC3-BBZ and GPC3-BBZ-NFAT-IL-7. The lentiviruses were packaged with 293T cells and transfected into healthy human T cells to prepare CAR-T cells， which were divided into non-transduced T cell (NT) group, GPC3-BBZ CAR-T cell group and GPC3-BBZ-NFAT-IL-7 CAR-T cell group. The expression of CAR in CAR-T cells of each group was determined by flow cytometry. IL-7 mRNA expression level in CAR-T cells activated by GPC3 protein was determined by qPCR. The proliferation ability of CAR-T cells under GPC3 antigen stimulation was evaluated by cell counting. The secretion levels of IL-7, IFN-γ, and TNF-α by CAR-T cells after stimulation with tumor cells was determined using ELISA. The cytotoxicity of CAR-T cells against human hepatocellular carcinoma Huh-7 cells was tested by real-time cell analyzer (RTCA). Results: Lentiviral vectors GPC3-BBZ and GPC3-BBZ-NFAT-IL-7 were successfully constructed, and GPC3-specific CAR-T cells were prepared. After activation with GPC3 antigen, GPC3-BBZ-NFAT-IL-7 CAR-T cells effectively expressed IL-7 mRNA (P < 0.01) and exhibited stronger proliferation capacity (P < 0.05). Compared with GPC3-BBZ CAR-T cells, GPC3-BBZ-NFAT-IL-7 CAR-T cells co-cultured with GPC3-positive Huh-7 cells secreted higher levels of IL-7, IFN-γ, and TNF-α (P < 0.01 or P < 0.001). The RTCA results showed that the cytotoxicity of GPC3-BBZ-NFAT-IL-7 CAR-T cells against GPC3-positive Huh-7 cells was significantly higher than that of GPC3-BBZ CAR-T cells (P < 0.05). Conclusion: GPC3-specific CAR-T cells with inducible IL-7 expression were successfully prepared, which exhibited immune activity and tumor cell killing capacity in vitro.
Abstract:
Objective: To investigate the anti-tumor effect of dendritic cells (DCs) vaccines loaded with shikonin (SK) and tumor cell lysate (TCL). Methods: DC vaccines of normal mouse origin loaded with SK and TCL were prepared in vitro. Fluorescence intensity of CD80 and CD86 on the surface of DCs was detected by flow cytometry. The expression of T-bet and RORγt in normal mouse splenic T cells co-cultured DCs that stimulated by SK + TCL was determined by flow cytometry, and the contents of IFN-γ, IL-12P70, and TNF-α in the co-culture supernatant were detected using ELISA. A Lewis lung cancer 3LL cell-bearing mouse model was established, and the mice were randomized into PBS + TCL group (PBS [1 mL] + TCL [5 × 105 cell/100 μL]), SK-L + TCL group (low SK concentration [1.25 mg/kg] + TCL), SK-M + TCL group (medium SK concentration [2.5 mg/kg] + TCL), and SK-H + TCL group (high SK concentration [5 mg/kg] + TCL), and paclitaxel (PTX) + TCL vaccine group (PTX [2 mg/kg] + TCL). Ten days after the end of vaccination, the solid tumor volume and survival rate of the mice were observed, and the killing capacity of splenic cytotoxic T lymphocytes (CTLs) was assessed by LDH assay. Results: DC vaccines loaded with SK + TCL showed high levels of CD80 and CD86 expression (both P < 0.01). The levels of IL-12P70, IFN- γ, and TNF- α in the DC-T cell co-culture supernatants were significantly increased (all P < 0.01), and the expression of T-bet and RORγt (both P < 0.01) in T cells were significantly elevated. A successful Lewis lung carcinoma mouse model was established, and the DC vaccines loaded with SK-H + TCL significantly delayed the growth of transplanted tumors and increased the mouse survival rate, while strongly inducing the cytotoxic activity of splenic CTLs (all P < 0.01). Conclusion: The SK + TCL-loaded DC vaccine can activate DCs to a mature state, up-regulate the expression of T-bet and RORγt in T cells, and initiate Th1 effector cells. SK shows promising antitumor effects in the treatment of Lewis lung carcinoma in mice.
Objective: To investigate the anti-tumor effect of dendritic cells (DCs) vaccines loaded with shikonin (SK) and tumor cell lysate (TCL). Methods: DC vaccines of normal mouse origin loaded with SK and TCL were prepared in vitro. Fluorescence intensity of CD80 and CD86 on the surface of DCs was detected by flow cytometry. The expression of T-bet and RORγt in normal mouse splenic T cells co-cultured DCs that stimulated by SK + TCL was determined by flow cytometry, and the contents of IFN-γ, IL-12P70, and TNF-α in the co-culture supernatant were detected using ELISA. A Lewis lung cancer 3LL cell-bearing mouse model was established, and the mice were randomized into PBS + TCL group (PBS [1 mL] + TCL [5 × 105 cell/100 μL]), SK-L + TCL group (low SK concentration [1.25 mg/kg] + TCL), SK-M + TCL group (medium SK concentration [2.5 mg/kg] + TCL), and SK-H + TCL group (high SK concentration [5 mg/kg] + TCL), and paclitaxel (PTX) + TCL vaccine group (PTX [2 mg/kg] + TCL). Ten days after the end of vaccination, the solid tumor volume and survival rate of the mice were observed, and the killing capacity of splenic cytotoxic T lymphocytes (CTLs) was assessed by LDH assay. Results: DC vaccines loaded with SK + TCL showed high levels of CD80 and CD86 expression (both P < 0.01). The levels of IL-12P70, IFN- γ, and TNF- α in the DC-T cell co-culture supernatants were significantly increased (all P < 0.01), and the expression of T-bet and RORγt (both P < 0.01) in T cells were significantly elevated. A successful Lewis lung carcinoma mouse model was established, and the DC vaccines loaded with SK-H + TCL significantly delayed the growth of transplanted tumors and increased the mouse survival rate, while strongly inducing the cytotoxic activity of splenic CTLs (all P < 0.01). Conclusion: The SK + TCL-loaded DC vaccine can activate DCs to a mature state, up-regulate the expression of T-bet and RORγt in T cells, and initiate Th1 effector cells. SK shows promising antitumor effects in the treatment of Lewis lung carcinoma in mice.
Abstract:
Objective: To develop a neoantigen peptide vaccine for personalized treatment of colorectal cancer (CRC), and to explore the feasibility and effectiveness of neoantigen peptide and its induced neoantigen reactive T cells (NRT) therapy for CRC. Methods: DNA and RNA were extracted from mouse CRC cell line CT26, followed by whole-exome and transcriptome sequencing to analyze tumor gene mutations and expression. Peptides with high immunogenicity were screened and synthesized through a machine learning based neoantigen prediction system. Mice were subcutaneously immunized with synthesized peptides, and the interferon (IFN)-γ level of splenocytes from immunized mice was determined using flow cytometry to screen peptides with strong immunogenicity. Afterwards, bone marrow-derived dendritic cells (BMDCs) loaded with immunogenic peptides were used to immunize mice bearing CRC model. The IFN-γ secretion ability by effector cells was determined by ELISPOT assay, and the cytotoxicity of γ secretion ability by effector cells was determined by ELISPOT assay, and the cytotoxicity of splenocytes from immunized mice was examined by time-resolved fluorescence immunoassay. In addition, the tumor growth and survival period of tumor-bearing mice were observed. Results: The neoantigen Glud1-V546I induced stronger IFN-γ secretion by NRT cells (P < 0.000 1). Compared with the wild peptide (Glud1-WT), Glud1-V546I induced higher IFN-γ secretion by NRT cells (P < 0.000 1) and stronger cytotoxicity (P < 0.000 1) in tumor-bearing mice. Meanwhile, Glud1-V546I significantly inhibited tumor growth (P < 0.001) and prolonged the survival of tumor-bearing mice (P < 0.01). Conclusion: The neoantigen peptide Glud1-V546I from mouse CT26 cells demonstrates effective anti-tumor responses in tumor-bearing mice, suggesting the potential for developing neoantigenbased personalized immunotherapies in CRC.
Objective: To develop a neoantigen peptide vaccine for personalized treatment of colorectal cancer (CRC), and to explore the feasibility and effectiveness of neoantigen peptide and its induced neoantigen reactive T cells (NRT) therapy for CRC. Methods: DNA and RNA were extracted from mouse CRC cell line CT26, followed by whole-exome and transcriptome sequencing to analyze tumor gene mutations and expression. Peptides with high immunogenicity were screened and synthesized through a machine learning based neoantigen prediction system. Mice were subcutaneously immunized with synthesized peptides, and the interferon (IFN)-γ level of splenocytes from immunized mice was determined using flow cytometry to screen peptides with strong immunogenicity. Afterwards, bone marrow-derived dendritic cells (BMDCs) loaded with immunogenic peptides were used to immunize mice bearing CRC model. The IFN-γ secretion ability by effector cells was determined by ELISPOT assay, and the cytotoxicity of γ secretion ability by effector cells was determined by ELISPOT assay, and the cytotoxicity of splenocytes from immunized mice was examined by time-resolved fluorescence immunoassay. In addition, the tumor growth and survival period of tumor-bearing mice were observed. Results: The neoantigen Glud1-V546I induced stronger IFN-γ secretion by NRT cells (P < 0.000 1). Compared with the wild peptide (Glud1-WT), Glud1-V546I induced higher IFN-γ secretion by NRT cells (P < 0.000 1) and stronger cytotoxicity (P < 0.000 1) in tumor-bearing mice. Meanwhile, Glud1-V546I significantly inhibited tumor growth (P < 0.001) and prolonged the survival of tumor-bearing mice (P < 0.01). Conclusion: The neoantigen peptide Glud1-V546I from mouse CT26 cells demonstrates effective anti-tumor responses in tumor-bearing mice, suggesting the potential for developing neoantigenbased personalized immunotherapies in CRC.
WU Wenqing, JIANG Longwei, JIA Shaochang, HU Jianhua, KE Chuanqing, ZHANG Haoli, FU Huiying, XIONG Xie
Abstract:
Objective: To explore the therapeutic effects and prognostic value of dendritic cell and cytokine-induced killer cell (DC-CIK) infusion in different routes in the treatment of intermediate and advanced primary liver cancer (PLC). Methods: A retrospective study was conducted on the clinical data of 69 patients with intermediate and advanced PLC treated with DC-CIK at the Oncology Department of the General Hospital of the Eastern Theater of Operations between October 2018 and September 2021. The patients were divided into a hepatic arterial infusion (HAI) group (n = 29) and an intravenous infusion (IV) group (n = 40) according to the different infusion modes used for DC-CIK treatment. The changes in peripheral blood T lymphocyte subsets (CD3+ , CD4+ , CD8+ T cells and CD4+ /CD8+ T cell ratio), cytokines (IL-2, IL-6, IFN-γ, and TNF-α), and alpha-fetoprotein (AFP) before and after treatment, treatment efficacy, overall survival (OS), and the incidence of adverse reactions were compared between the two groups. Results: After DC-CIK treatment, the objective remission rate (ORR) was 0%, and the disease control rate (DCR) was 75.8% in the HAI group; the ORR was 0%, and the DCR was 72.5% in the IV group (all P > 0.05). There were no significant changes in T-lymphocyte subpopulation between the two groups before and after treatment (all P > 0.05). The mean levels of peripheral blood IL-2, IL-6, IFN- γ and TNF- α after treatment were significantly higher than those before treatment in both groups (all P < 0.01), but with no significant difference between the two groups (all P > 0.05). The mean OS in HAI group was 48.17 months, and the OS in IV group was 39.65 months, with no significant difference between the two groups (P > 0.05). No severe adverse reactions occurred during the treatment. Conclusion: Autologous DC-CIK treatment via HAI is safe and effective for PLC. Compared to IV treatment, it tends to further improve the clinical benefit, which is worthy of clinical reference.
Objective: To explore the therapeutic effects and prognostic value of dendritic cell and cytokine-induced killer cell (DC-CIK) infusion in different routes in the treatment of intermediate and advanced primary liver cancer (PLC). Methods: A retrospective study was conducted on the clinical data of 69 patients with intermediate and advanced PLC treated with DC-CIK at the Oncology Department of the General Hospital of the Eastern Theater of Operations between October 2018 and September 2021. The patients were divided into a hepatic arterial infusion (HAI) group (n = 29) and an intravenous infusion (IV) group (n = 40) according to the different infusion modes used for DC-CIK treatment. The changes in peripheral blood T lymphocyte subsets (CD3+ , CD4+ , CD8+ T cells and CD4+ /CD8+ T cell ratio), cytokines (IL-2, IL-6, IFN-γ, and TNF-α), and alpha-fetoprotein (AFP) before and after treatment, treatment efficacy, overall survival (OS), and the incidence of adverse reactions were compared between the two groups. Results: After DC-CIK treatment, the objective remission rate (ORR) was 0%, and the disease control rate (DCR) was 75.8% in the HAI group; the ORR was 0%, and the DCR was 72.5% in the IV group (all P > 0.05). There were no significant changes in T-lymphocyte subpopulation between the two groups before and after treatment (all P > 0.05). The mean levels of peripheral blood IL-2, IL-6, IFN- γ and TNF- α after treatment were significantly higher than those before treatment in both groups (all P < 0.01), but with no significant difference between the two groups (all P > 0.05). The mean OS in HAI group was 48.17 months, and the OS in IV group was 39.65 months, with no significant difference between the two groups (P > 0.05). No severe adverse reactions occurred during the treatment. Conclusion: Autologous DC-CIK treatment via HAI is safe and effective for PLC. Compared to IV treatment, it tends to further improve the clinical benefit, which is worthy of clinical reference.
Abstract:
Objective: To investigate the effects of four-and-a-half LIM domains 2 (FHL2) on glioma cell proliferation and its molecular mechanisms. Methods: The relationship between FHL2 mRNA expression levels in gliomas and patient prognosis was analyzed using TCGA and CGGA databases. The protein expression levels of FHL2 in collected human glioma tissue samples and human glioma cell lines (U87, T98G, U251, SNB19, GSC23, A172, LN229, G267), and astrocyte NHA were analyzed using Western blot (WB). Lentiviral vecors were used to construct U87 cells with stable FHL2 knockdown and SNB19 cells overexpressing FHL2, namely U87-shGFP, U87-shFHL2-1#, U87-shFHL2-4#, and SNB19-3flag, SNB19-3flag-FHL2 groups. The effects of FHL2 knockdown and overexpression on cell proliferation were assessed using CCK-8 assays and colony formation assay. Coimmunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC/MS) were employed to identify proteins interacting with FHL2 in glioma cells, and Co-IP and immunofluorescence were used to verify their binding and co-localization. Changes in intracellular lactate production and lactate dehydrogenase (LDH) activity following FHL2 knockdown and overexpression were measured using a microplate reader. WB was used to analyze the protein expression levels of FHL2, LDHA, and p-LDHA in normal brain tissues and glioma tissues, as well as their relationships. The small molecule inhibitor of LDHA, AT-101, was used to treat SNB19 cells overexpressing FHL2. The role of FHL2 in glioma lactate metabolism and the potential therapeutic effect of AT-101 in glioma were validated using CCK-8 assays and colorimetric assays with a microplate reader. Results: Co-IP and LC/MS analyses revealed an interaction between FHL2 and LDHA in glioma cells. Overexpression of FHL2 increased LDHA activity and lactate production (all P < 0.001), thereby promoting glioma cell proliferation (P < 0.001 or P < 0.001). Conversely, knockdown of FHL2 reduced LDHA activity and lactate production (P < 0.001, P < 0.05) and inhibited cell growth (P < 0.01). AT101 inhibited LDHA activity and significantly suppressed FHL2-induced glioma cell proliferation while restoring phosphorylated LDHA (Y10) levels (P < 0.01, P < 0.001). Conclusion: FHL2 interacts with LDHA protein, and FHL2 promotes LDHA activity and lactic acid production by activating the expression of p-LDHA (Y10), thus facilitating the proliferation of glioma cells. Targeting this interaction may become a potential strategy for treating gliomas.
Objective: To investigate the effects of four-and-a-half LIM domains 2 (FHL2) on glioma cell proliferation and its molecular mechanisms. Methods: The relationship between FHL2 mRNA expression levels in gliomas and patient prognosis was analyzed using TCGA and CGGA databases. The protein expression levels of FHL2 in collected human glioma tissue samples and human glioma cell lines (U87, T98G, U251, SNB19, GSC23, A172, LN229, G267), and astrocyte NHA were analyzed using Western blot (WB). Lentiviral vecors were used to construct U87 cells with stable FHL2 knockdown and SNB19 cells overexpressing FHL2, namely U87-shGFP, U87-shFHL2-1#, U87-shFHL2-4#, and SNB19-3flag, SNB19-3flag-FHL2 groups. The effects of FHL2 knockdown and overexpression on cell proliferation were assessed using CCK-8 assays and colony formation assay. Coimmunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC/MS) were employed to identify proteins interacting with FHL2 in glioma cells, and Co-IP and immunofluorescence were used to verify their binding and co-localization. Changes in intracellular lactate production and lactate dehydrogenase (LDH) activity following FHL2 knockdown and overexpression were measured using a microplate reader. WB was used to analyze the protein expression levels of FHL2, LDHA, and p-LDHA in normal brain tissues and glioma tissues, as well as their relationships. The small molecule inhibitor of LDHA, AT-101, was used to treat SNB19 cells overexpressing FHL2. The role of FHL2 in glioma lactate metabolism and the potential therapeutic effect of AT-101 in glioma were validated using CCK-8 assays and colorimetric assays with a microplate reader. Results: Co-IP and LC/MS analyses revealed an interaction between FHL2 and LDHA in glioma cells. Overexpression of FHL2 increased LDHA activity and lactate production (all P < 0.001), thereby promoting glioma cell proliferation (P < 0.001 or P < 0.001). Conversely, knockdown of FHL2 reduced LDHA activity and lactate production (P < 0.001, P < 0.05) and inhibited cell growth (P < 0.01). AT101 inhibited LDHA activity and significantly suppressed FHL2-induced glioma cell proliferation while restoring phosphorylated LDHA (Y10) levels (P < 0.01, P < 0.001). Conclusion: FHL2 interacts with LDHA protein, and FHL2 promotes LDHA activity and lactic acid production by activating the expression of p-LDHA (Y10), thus facilitating the proliferation of glioma cells. Targeting this interaction may become a potential strategy for treating gliomas.
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2012,19(5):550-555, DOI: 10.3872/j.issn.1007-385X.2012.5.018
Abstract:
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
2016,23(2):149-160, DOI: 10.3872/j.issn.1007-385X.2016.02.001
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
2018,25(1):23-27, DOI: 10.3872/j.issn.1007-385X.2018.01.004
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
2010,17(1):57-61, DOI: 10.3872/j.issn.1007-385X.2010.1.011
Abstract:
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
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Chinese Journal Of Cancer Biotheray ® 2024 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2024 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.