Latest ArticlesAs a critical part of the lifecycle management of biological products, post-approval changes may bring potential impact on the quality of biological products. Compared with other therapeutic products, prophylactic vaccines show different emphasis on regulatory requirements, product characteristics, manufacturing quality control, etc. so there are special considerations on the research and registration of post-approval changes. Aiming to help vaccine applicants increase knowledge about post-approval changes, the technical requirements on post-approval change of vaccine products and other biological products are compared and analyzed in this paper, and some special considerations for the study of post-approval change of vaccine are refined.
Neoantigens are a class of specific polypeptides produced by gene mutations in tumor cells, which can be expressed and processed in cells. They are subsequently presented to the cell surface by major histocompatibility complexes and recognized by T cells, thus activating the body's immune system and initiating a series of immune responses. Due to the rapid development of sequencing technology and artificial intelligence prediction methods, neoantigen-based tumor immunotherapy has emerged as a promising approach for future cancer treatment. In the era of precision medicine, neoantigen-based personalized tumor vaccines and adoptive T cell transfer therapy have shown encouraging results in the treatment of malignant melanoma, brain glioma and other tumors. Furthermore, the combination of neoantigens with other immunotherapies shows significant potential for application. However, as a new personalized treatment approach, its development and regulation are facing numerous challenges. In this article, we briefly introduce the research progress and regulatory status of neoantigens in order to provide reference for the research and development and regulation of neoantigens in China.
Autologous chimeric antigen receptor T cell (CAR-T) cell therapy products have brought significant survival benefits to tumor patients, especially in the treatment of hematologic tumors. However, the common production mode of autologous CAR-T therapy products is complicated and has a long cycle. As a result, the production capacity of this kind of products has limited their clinical application to a certain extent. In this paper, based on the analysis of the common production mode of autologous CAR-T cell products, the content and evaluation of the capacity confirmation study and capacity change study of autologous CAR-T therapeutic products are proposed in combination with the current research progress, hoping to effectively promote the development and clinical application of such products.
Based on the requirement on the experimental data in the pharmaceutical patent examination of China National Intellectual Property Office (CNIPA), some recent administrative decisions of CNIPA, the repetition of experimental data in the development of some "blockbuster" drugs, and the relevant cases of the US Federal Circuit, this paper discusses the two sides of supplementary experimental data in pharmaceutical patent protection.
Small cell lung cancer (SCLC) is characterized by a high degree of malignancy, with poor prognosis and high-growth fraction. About two-thirds of patients have developed distant metastasis at the time of diagnosis with rapid disease progression and high recurrence rates. Currently, topotecan-based chemotherapy remains the standard second-line treatment of SCLC with unfavorable disease remission, and less than one-fourth of patients have benefited from its efficacy. Chemotherapy-induced myelosuppression (CIM) is the most common toxicity in cancer chemotherapy, and severe CIM will reduce the dose intensity and anti-tumor efficacy of chemotherapy. Trilaciclib is a short-acting intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor administered prior to chemotherapy to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy, which has been approved by NMPA for prevention of CIM in SCLC in July 2022. Previous results showed that trilaciclib yielded favorable bone marrow protection during chemotherapy, but its anti-tumor effects in second-line treatment of SCLC have not been determined. This paper reports a case of a patient with advanced small-cell lung cancer with multiple metastases who obtained progression-free survival time of more than 1 year using trilaciclib combined with topotecan as second-line treatment.
Non-alcoholic fatty liver disease (NAFLD) is a common chronic metabolic disease characterized by the accumulation of fat in the liver. The onset and progression of NAFLD are associated with a variety of metabolic abnormalities, including obesity, diabetes mellitus, and hyperlipidemia. Due to its high prevalence and risk worldwide, NAFLD has become an important issue in public health. However, to date, treatments for NAFLD are very limited, with no relevant drugs approved for marketing in Europe, America, or China and clinical trials of new drugs have gained no progress in recent years. This paper reviews the therapeutic targets, clinical research progress of new drugs, and new treatment strategies for NAFLD, in addition to summarizing the reasons for the high failure rate of NASH clinical trials and proposing corresponding solutions, aiming at providing ideas and reference for new drug development.
To investigate the in vivo and in vitro antibacterial activity of doxycycline combined with levofloxacin on carbapenem-resistant Klebsiella pneumoniae (CRKP).
Eight clinically isolated CRKP strains were collected in Yichun People's Hospital, and the minimum inhibitory concentration (MIC) of 8 CRKPs was determined using microbroth dilution method in vitro. The antibacterial effect of the two drugs was judged by checkerboard dilution method. The time-sterilization curve was further applied to evaluate the combined bactericidal effect of the two drugs. Crystal violet staining semi-quantitative biofilm method was used to determine the inhibitory effect and elimination effect of the combination of two drugs on biofilm formation. In vivo, a model of acute lung infection of mice was established by nasal instillation of CRKP bacteria, and the mental state of mice was recorded. The bacterial load of lung tissues, the levels of serum inflammatory factor C-reactive protein (CRP), IL-6 and pathological morphological changes were evaluated and analyzed.
The MIC of doxycycline to 8 CRKP strains was 4~256 ug·mL-1, levofloxacin to 8 strains of CRKP MIC of 16~256 ug·mL-1. The checkerboard method showed that doxycycline combined with levofloxacin had an 80% synergistic or additive effect on 8 CRKP strains. The time-sterilization curve showed that after the treatment of doxycycline combined with levofloxacin on CRKP2 and CRKP7 for 24 hours, the number of bacteria decreased by ≥2 lg CFU·mL-1 compared with the initial bacterial number, showing bacteriostatic or bactericidal effects. The results of crystal violet staining showed that the combination of doxycycline and levofloxacin had inhibitory and destructive effects on CRKP biofilms. Animal experiments showed that compared with the model group, the combined group mice had a good mental state, and the loading levels of lung tissue, C-reactive protein (CRP) and IL-6 significantly reduced (P<0.001). The results of HE staining showed that the alveolar structure was clear, the inflammatory cells reduced, and the hyperemia area reduced in the drug administration group compared with the model group, and the differences were statistically significant (P<0.001).
In vitro experiments show that doxycycline combined with levofloxacin has a synergistic antibacterial or bactericidal effect on CRKP, and in vivo experiments show that doxycycline combined with levofloxacin can reduce inflammatory indexes, effectively treat bacterial infections in lung tissue, exerting good antibacterial effect in vivo.
To analyze the pattern, characteristics and causes of protocol violation in anti-tumor drug clinical trials from the perspective of ethical review. The number and categories of violation projects were retrospectively analyzed and compared in different departments and the area of clinical trials (domestic or international). The impact of protocol violation on clinical trials carried out in our hospital from 2018 to 2021 was also analyzed. From 2018 to 2021, 1256 protocol violation cases occurred in clinical trials of anti-tumor drugs carried out in our hospital. The number of continuous protocol violations (318, 25.32%) was the largest, and the number of researchers' failure to cooperate with supervision/audit (6, 0.50%) was the fewest. The difference in the number of protocol violation between internal and surgical, domestic and global clinical trials were both statistically significant (P<0.01). The proportion of protocol violations affecting the safety, rights of subjects and trials results were 5.81%, 4.78% and 5.41%, respectively. Various protocol violations may occur during clinical trials of anti-tumor drugs. In order to improve the quality of clinical trials, it can be effectively avoided by strengthening quality control and conducting targeted training for the research team and subjects.
Immunotherapy combined with chemotherapy has been established as the standard first-line treatment in advanced esophageal cancer (EC). Myelosuppression is the most common side effects of chemotherapy, and severe myelosuppression often leads to prolonged cycles of chemotherapy and reduced doses of chemotherapy, thereby reducing the intensity and potential anti-tumor efficacy of chemotherapy. At present, granulocyte-stimulating factor (G-CSF) is widely used to stimulate the differentiation of bone marrow hematopoietic progenitor cells to treat chemotherapy-induced myelosuppression (CIM). Trilaciclib is a short-acting and reversible CDK4/6 inhibitor, which can provide systemic protection of bone marrow hematopoiesis, and was approved by NMPA in July 2022 for the prophylactic treatment of myelosuppression in extensive-stage small cell lung cancer (ES-SCLC). However, trilaciclib has not been widely used in clinical practice. Therefore, this paper reports a case of one patient with advanced EC who was treated by trilaciclib to prevent CIM in our department, aiming to provide further reference and basis for further investigation.
Molecular targeted therapy has become a research hotspot in the field of cancer therapy in recent years. Regorafenib belongs to the multi-target tyrosine kinase inhibitor class of antitumor drug developed by Bayer company, which was approved by NMPA in March 2017. This article introduces the status of regorafenib-related Chinese patent applications and focuses on combing and analyzing the development context of patent technology, in order to provide reference for the drug R&D and patent portfolio for relevant domestic pharmaceutical companies.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
