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Abstract:
Chimeric antigen receptor gene-modified T-cell (CAR-T cell), represented by the target CD19, has achieved breakthrough progress in the treatment of B-cell malignancies. However, with the increasing number of patients undergoing CAR-T cell therapy, the issue of relapse and resistance has become particularly prominent and is now a major clinical challenge and a research hotspot in the field. In recent years, in addition to immune escape due to antigen loss and treatment insensitivity caused by CAR-T cells dysfunction, progress has been made in understanding resistance mechanisms caused by intrinsic factors of tumor cells. Using high throughput screening system, resistance mechanisms mediated by downregulation or deficient expression of pro-apoptotic molecules (such as NOXA, FADD) and adhesion molecules (such as CD58, ICAM1) have been identified. Several strategies have been developed to reverse these resistance mechanisms, such as HDAC inhibitors combined with CAR-T cell therapy to treat NOXA-low expressing nonHodgkin lymphoma; pretreatment of CAR-T cells with epigenetic drugs to enhance their antitumor efficacy and persistence; using gene editing technologies to relieve gene suppression and enhance CAR-T cell activity; and overexpressing cytokines to improve tumor microenvironment. Some of these strategies have already been clinically validated. This review aims to summarize the existing resistance mechanisms to CAR-T cell therapy and their targeted reversal strategies, analyze the clinical outcomes of related studies, and provide new insights into enhancing CAR-T cell efficacy in B-cell malignancies.
Chimeric antigen receptor gene-modified T-cell (CAR-T cell), represented by the target CD19, has achieved breakthrough progress in the treatment of B-cell malignancies. However, with the increasing number of patients undergoing CAR-T cell therapy, the issue of relapse and resistance has become particularly prominent and is now a major clinical challenge and a research hotspot in the field. In recent years, in addition to immune escape due to antigen loss and treatment insensitivity caused by CAR-T cells dysfunction, progress has been made in understanding resistance mechanisms caused by intrinsic factors of tumor cells. Using high throughput screening system, resistance mechanisms mediated by downregulation or deficient expression of pro-apoptotic molecules (such as NOXA, FADD) and adhesion molecules (such as CD58, ICAM1) have been identified. Several strategies have been developed to reverse these resistance mechanisms, such as HDAC inhibitors combined with CAR-T cell therapy to treat NOXA-low expressing nonHodgkin lymphoma; pretreatment of CAR-T cells with epigenetic drugs to enhance their antitumor efficacy and persistence; using gene editing technologies to relieve gene suppression and enhance CAR-T cell activity; and overexpressing cytokines to improve tumor microenvironment. Some of these strategies have already been clinically validated. This review aims to summarize the existing resistance mechanisms to CAR-T cell therapy and their targeted reversal strategies, analyze the clinical outcomes of related studies, and provide new insights into enhancing CAR-T cell efficacy in B-cell malignancies.
Abstract:
Immunotherapy is propelling the field of anti-tumor treatment into a new era, with neoantigen vaccine serving as a pioneering force in immunotherapy. These vaccines are advancing their basic research and clinical trials at an unprecedented speed, yielding promising results and demonstrating substantial development potential. This review focuses on the latest progress in neoantigen vaccine research, with detailed introduction to the two major highlights: long peptide vaccines and mRNA vaccines. Peptide vaccines have attracted attention for their efficient production and scalability, though their rapid degradation poses a challenge. Advances in nanocarrier technologies help mitigate this limitation, and long-peptide vaccines have demonstrated promising efficacy in patients with various solid tumors, including melanoma and glioblastoma. Additionally, nanoparticle-based short peptide vaccines have demonstrated advantages in adjuvant gastric cancer therapy. mRNA vaccines, widely recognized for their application in COVID-19, have become a hotspot in cancer vaccine development due to their safety and ability to encode multiple antigens. For example, RNA vaccines encoding various KRAS mutations have shown favorable outcomes in pancreatic cancer. Furthermore, several studies suggest that combining neoantigen vaccines with immune checkpoint inhibitors or adoptive cell therapies can exert synergistic effects, further enhancing efficacy. This article delves into the challenges faced by neoantigen vaccines in the clinical translation phase and, based on this, actively explores and discusses potential strategies to address these challenges. The aim is to inspire new ideas and pave the way for future advancements in neoantigen vaccine development.
Immunotherapy is propelling the field of anti-tumor treatment into a new era, with neoantigen vaccine serving as a pioneering force in immunotherapy. These vaccines are advancing their basic research and clinical trials at an unprecedented speed, yielding promising results and demonstrating substantial development potential. This review focuses on the latest progress in neoantigen vaccine research, with detailed introduction to the two major highlights: long peptide vaccines and mRNA vaccines. Peptide vaccines have attracted attention for their efficient production and scalability, though their rapid degradation poses a challenge. Advances in nanocarrier technologies help mitigate this limitation, and long-peptide vaccines have demonstrated promising efficacy in patients with various solid tumors, including melanoma and glioblastoma. Additionally, nanoparticle-based short peptide vaccines have demonstrated advantages in adjuvant gastric cancer therapy. mRNA vaccines, widely recognized for their application in COVID-19, have become a hotspot in cancer vaccine development due to their safety and ability to encode multiple antigens. For example, RNA vaccines encoding various KRAS mutations have shown favorable outcomes in pancreatic cancer. Furthermore, several studies suggest that combining neoantigen vaccines with immune checkpoint inhibitors or adoptive cell therapies can exert synergistic effects, further enhancing efficacy. This article delves into the challenges faced by neoantigen vaccines in the clinical translation phase and, based on this, actively explores and discusses potential strategies to address these challenges. The aim is to inspire new ideas and pave the way for future advancements in neoantigen vaccine development.
Abstract:
Immunotherapy has revolutionized clinical treatment of solid tumors, becoming a core strategy for the treatment of solid tumors. Currently approved immunotherapy strategies for solid tumors include PD-1 antibodies, CTLA-4 antibodies, bispecific antibodies, TCR-T cells, and TIL. These approaches primarily exert antitumor effects by activating T-cell-mediated immune responses or directly supplementing tumor-reactive T cells. However, restrained by inhibitory factors within the tumor microenvironment, the therapeutic outcomes of these strategies remain suboptimal. Based on the cancer-immunity cycle theory, this article provides a systematic review of approved immunotherapy strategies, early-stage clinical trials, and emerging immunotherapy approaches. It also offers insights into the future directions of immunotherapy targeting T cells and other cell populations beyond T cells.
Immunotherapy has revolutionized clinical treatment of solid tumors, becoming a core strategy for the treatment of solid tumors. Currently approved immunotherapy strategies for solid tumors include PD-1 antibodies, CTLA-4 antibodies, bispecific antibodies, TCR-T cells, and TIL. These approaches primarily exert antitumor effects by activating T-cell-mediated immune responses or directly supplementing tumor-reactive T cells. However, restrained by inhibitory factors within the tumor microenvironment, the therapeutic outcomes of these strategies remain suboptimal. Based on the cancer-immunity cycle theory, this article provides a systematic review of approved immunotherapy strategies, early-stage clinical trials, and emerging immunotherapy approaches. It also offers insights into the future directions of immunotherapy targeting T cells and other cell populations beyond T cells.
Abstract:
Despite significant improvements in survival among lung cancer patients treated with PD-1/PD-L1 inhibitor-based immunotherapy, the issue of drug resistance remains a major challenge. This article delineates the definition, mechanisms, and predictive models of immunotherapy resistance, and introduces therapeutic strategies to address resistance, including continued use of immunotherapy, rechallenge, local treatment combined with systemic immunotherapy in the context of oligometastasis, and combination therapy after extensive progression. Furthermore, it explores the application prospects of novel therapeutic approaches such as adoptive cell therapy, antibody-drug conjugates, bispecific antibodies, and tumor vaccines in overcoming drug resistance. Additionally, the article summarizes the challenges and development directions of immunotherapy for lung cancer, emphasizing the importance of ongoing research, innovative treatment strategies, and interdisciplinary collaboration. These efforts aim to provide new ideas and research directions for achieving personalized, precise, and efficient lung cancer treatment in the future.
Despite significant improvements in survival among lung cancer patients treated with PD-1/PD-L1 inhibitor-based immunotherapy, the issue of drug resistance remains a major challenge. This article delineates the definition, mechanisms, and predictive models of immunotherapy resistance, and introduces therapeutic strategies to address resistance, including continued use of immunotherapy, rechallenge, local treatment combined with systemic immunotherapy in the context of oligometastasis, and combination therapy after extensive progression. Furthermore, it explores the application prospects of novel therapeutic approaches such as adoptive cell therapy, antibody-drug conjugates, bispecific antibodies, and tumor vaccines in overcoming drug resistance. Additionally, the article summarizes the challenges and development directions of immunotherapy for lung cancer, emphasizing the importance of ongoing research, innovative treatment strategies, and interdisciplinary collaboration. These efforts aim to provide new ideas and research directions for achieving personalized, precise, and efficient lung cancer treatment in the future.
Abstract:
Nonsense-mediated mRNA decay (NMD) serves as a quality control mechanism, degrading aberrant mRNAs with premature termination codons (PTCs). It also plays a role in growth and development, immune regulation, and is closely associated with the tumor microenvironment. NMD has a dual role in cancer; on the one hand, it inhibits tumor progression through down-regulation of pro-oncogenic protein expression, inhibition of pro-oncogenic signaling pathways and stressful microenvironments, while one the other hand, it promotes tumor progression by inhibiting oncogene expression, cancer cell apoptosis and tumor neoantigen production. Notably, NMD does not degrade all PTC-containing mRNAs. The location of the PTC may determine whether NMD is triggered or evaded. Since different genes vary greatly in high-frequency mutation regions, the likelihood of triggering NMD after a PTC mutation differs across genes. With the maturation and widespread use of second-generation sequencing technology, gene mutation screening has become a routine clinical diagnostic tool, making it possible to explore the patterns and significance of NMD from a multi-gene perspective. By further understanding the functions and mechanisms of NMD and assessing the NMD levels through high-throughput sequencing and computational algorithms, its potential clinical value is expected to be revealed, contributing to the advancement of personalized treatment and precision medicine.
Nonsense-mediated mRNA decay (NMD) serves as a quality control mechanism, degrading aberrant mRNAs with premature termination codons (PTCs). It also plays a role in growth and development, immune regulation, and is closely associated with the tumor microenvironment. NMD has a dual role in cancer; on the one hand, it inhibits tumor progression through down-regulation of pro-oncogenic protein expression, inhibition of pro-oncogenic signaling pathways and stressful microenvironments, while one the other hand, it promotes tumor progression by inhibiting oncogene expression, cancer cell apoptosis and tumor neoantigen production. Notably, NMD does not degrade all PTC-containing mRNAs. The location of the PTC may determine whether NMD is triggered or evaded. Since different genes vary greatly in high-frequency mutation regions, the likelihood of triggering NMD after a PTC mutation differs across genes. With the maturation and widespread use of second-generation sequencing technology, gene mutation screening has become a routine clinical diagnostic tool, making it possible to explore the patterns and significance of NMD from a multi-gene perspective. By further understanding the functions and mechanisms of NMD and assessing the NMD levels through high-throughput sequencing and computational algorithms, its potential clinical value is expected to be revealed, contributing to the advancement of personalized treatment and precision medicine.
Abstract:
Objective: To investigate the influence of SOX9 on the proliferation, migration, invasion, and stemness of laryngeal squamous cell carcinoma (LSCC) cells by upregulating the expression of long non-coding RNA LINC01503. Methods: Human LSCC cells AMC-HN-8, TU177, TU212, and TU686 were cultured routinely. Control nucleic acids (NC) and knockdown sequences (si-SOX9- NC, si-SOX9#1, si-SOX9#2, si-LINC01503-NC, si-LINC01503#1, si-LINC01503#2) or overexpression plasmids (pcDNA3.1-SOXNC, pcDNA3.1-SOX-oe, pcDNA3.1-LIN01503-NC, and pcDNA3.1-LIN01503-oe) were transfected into TU177 cells or TU686 cells. These groups were named as si-SOX9-NC group, si-SOX9#1 group, si-SOX9#2 group, si-LINC01503-NC group, si-LINC01503#1 group, si-LINC01503#2 group; pcDNA3.1-SOX9-NC group, pcDNA3.1-SOX9-oe group, pcDNA3.1-LINC01503-NC group, pcDNA3.1-LINC01503-oe group, si-SOX9-NC + pcDNA3.1-LINC01503-NC group, and si-SOX9 + pcDNA3.1-LINC01503-oe group. The expression of SOX9 mRNA and LINC01503 in each group of cells was detected by qPCR. Bioinformatics tool was employed to identify the binding site of SOX9 to lncRNA LINC01503 promoter region. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene experiments were carried out to validate the binding between SOX9 and the LINC01503 promoter. SOX9 knockdown efficiency and the influence of LINC01503 on the expression of stem cell markers in TU177 and TU686 cells were detected by WB assay. MTS assay was used to detect cell proliferation, scratch wound healing, and Transwell assays assessed cell migration, while colony formation assays evaluated the ability of cells to form colonies. Results: SOX9 was highly expressed in all LSCC cells (R = 0.12, P < 0.05). Database analysis showed a positive correlation between SOX9 and LINC01503 expression in head and neck squamous cell carcinoma (P = 0.005 9). It was proved that SOX9 directly binds with the LINC01503 promoter and promotes its transcriptional expression (P < 0.05). Knockdown of LINC01503 significantly suppressed the proliferation, migration, and invasion of TU177 cells (all P<0.05). Overexpression of LINC01503 notably enhanced the proliferation, migration, invasion and colony formation of TU686 cells (all P<0.05), as well as the expression of cell stemness markers CD133, OCT4, and SOX2 at both mRNA and protein levels (all P<0.05). However, knockdown of LINC01503 inhibited colony formation and expression of stem cell markers in TU686 cells (P < 0.05). Knockdown of SOX9 significantly suppressed the proliferation, migration, and invasion ability of TU177 cells and reduced the expression of their stem cell markers (all P<0.05). Meanwhile, overexpression of LINC01503 partially reversed the inhibitory effect of SOX9 knockdown on the malignant biological behavior and stem cell marker expression in TU177 cells (all P < 0.05). Conclusion: Both SOX9 and LINC01503 are highly expressed in LSCC cells. SOX9 may promote the proliferation, migration, invasion and stemness of laryngeal squamous cell carcinoma by upregulating LINC01503 expression.
Objective: To investigate the influence of SOX9 on the proliferation, migration, invasion, and stemness of laryngeal squamous cell carcinoma (LSCC) cells by upregulating the expression of long non-coding RNA LINC01503. Methods: Human LSCC cells AMC-HN-8, TU177, TU212, and TU686 were cultured routinely. Control nucleic acids (NC) and knockdown sequences (si-SOX9- NC, si-SOX9#1, si-SOX9#2, si-LINC01503-NC, si-LINC01503#1, si-LINC01503#2) or overexpression plasmids (pcDNA3.1-SOXNC, pcDNA3.1-SOX-oe, pcDNA3.1-LIN01503-NC, and pcDNA3.1-LIN01503-oe) were transfected into TU177 cells or TU686 cells. These groups were named as si-SOX9-NC group, si-SOX9#1 group, si-SOX9#2 group, si-LINC01503-NC group, si-LINC01503#1 group, si-LINC01503#2 group; pcDNA3.1-SOX9-NC group, pcDNA3.1-SOX9-oe group, pcDNA3.1-LINC01503-NC group, pcDNA3.1-LINC01503-oe group, si-SOX9-NC + pcDNA3.1-LINC01503-NC group, and si-SOX9 + pcDNA3.1-LINC01503-oe group. The expression of SOX9 mRNA and LINC01503 in each group of cells was detected by qPCR. Bioinformatics tool was employed to identify the binding site of SOX9 to lncRNA LINC01503 promoter region. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene experiments were carried out to validate the binding between SOX9 and the LINC01503 promoter. SOX9 knockdown efficiency and the influence of LINC01503 on the expression of stem cell markers in TU177 and TU686 cells were detected by WB assay. MTS assay was used to detect cell proliferation, scratch wound healing, and Transwell assays assessed cell migration, while colony formation assays evaluated the ability of cells to form colonies. Results: SOX9 was highly expressed in all LSCC cells (R = 0.12, P < 0.05). Database analysis showed a positive correlation between SOX9 and LINC01503 expression in head and neck squamous cell carcinoma (P = 0.005 9). It was proved that SOX9 directly binds with the LINC01503 promoter and promotes its transcriptional expression (P < 0.05). Knockdown of LINC01503 significantly suppressed the proliferation, migration, and invasion of TU177 cells (all P<0.05). Overexpression of LINC01503 notably enhanced the proliferation, migration, invasion and colony formation of TU686 cells (all P<0.05), as well as the expression of cell stemness markers CD133, OCT4, and SOX2 at both mRNA and protein levels (all P<0.05). However, knockdown of LINC01503 inhibited colony formation and expression of stem cell markers in TU686 cells (P < 0.05). Knockdown of SOX9 significantly suppressed the proliferation, migration, and invasion ability of TU177 cells and reduced the expression of their stem cell markers (all P<0.05). Meanwhile, overexpression of LINC01503 partially reversed the inhibitory effect of SOX9 knockdown on the malignant biological behavior and stem cell marker expression in TU177 cells (all P < 0.05). Conclusion: Both SOX9 and LINC01503 are highly expressed in LSCC cells. SOX9 may promote the proliferation, migration, invasion and stemness of laryngeal squamous cell carcinoma by upregulating LINC01503 expression.
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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 ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.