Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens.

Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies in situ, resulting in an efficacious and tumor-specific therapeutic effect.

Bibliometric analysis of oncolytic virus research, 2000 to 2018.

BACKGROUND: Accumulating evidence in the last decade has pointed to the effectiveness of oncolytic virus in the treatment of a variety of cancer types in preclinical or clinical studies, showing high potency and low toxicity compared to conventional treatments. To track this research trend and highlight future directions, we conducted a bibliometric analysis of oncolytic virus research to date. METHODS: Relevant studies were obtained from the Web of Science Core Collection between January 2000 and December 2018. Data were collected in terms of the number of publications, country, journal of publication, journal scope, author, and keywords or topics. Analysis and visual representation of the data were performed with CiteSpace V. RESULTS: The trend in publications related to oncolytic virus showed a dramatic increase, from 10 publications in 2000 to 199 publications in 2018. The United States clearly dominates this field (981 publications, 52.770%), followed by Canada (244, 13.125%) and China (205, 11.027%). The top 15 academic journals account for over one third of the total publications on oncolytic virus research (724, 38.95%). Most of the related papers were published in journals with a focus on biology, medicine, immunology, medicine, molecular biology, and clinical perspectives, as represented by the dual-map overlay. The most highly cited papers were published in journals in the fields of nursing, molecular biology, general biology, genetics, health, and medicine. Over 1300 institutions have focused their attention on oncolytic virus research to date, and cooperation among mainstream institutions is common. CONCLUSION: The global field of oncolytic virus research has expanded at a rapid pace from 2000 to 2018. There is no doubt that North America currently has the most powerful impact on the field with respect to both productivity and contribution. However, European and some East Asian institutions are also prominent in this field. Overall, this bibliometric study identifies the top 4 hotspots in oncolytic virus research: T-cells, vaccinia virus, dendritic cells, and apoptosis. Thus, further research focuses on these topics may be more helpful to promote the clinical translation of this treatment strategy to bring a benefit to cancer patients in the near future.

A novel approach for rapid high-throughput selection of recombinant functional rat monoclonal antibodies.

BACKGROUND: Most monoclonal antibodies against mouse antigens have been derived from rat spleen-mouse myeloma fusions, which are valuable tools for purposes ranging from general laboratory reagents to therapeutic drugs, and yet selecting and expressing them remains a time-consuming and inefficient process. Here, we report a novel approach for the rapid high-throughput selection and expression of recombinant functional rat monoclonal antibodies with different isotypes. RESULTS: We have developed a robust system for generating rat monoclonal antibodies through several processes involving simultaneously immunizing rats with three different antigens expressing in a mixed cell pools, preparing hybridoma cell pools, in vitro screening and subsequent cloning of the rearranged light and heavy chains into a single expression plasmid using a highly efficient assembly method, which can decrease the time and effort required by multiple immunizations and fusions, traditional clonal selection and expression methods. Using this system, we successfully selected several rat monoclonal antibodies with different IgG isotypes specifically targeting the mouse PD-1, LAG-3 or AFP protein from a single fusion. We applied these recombinant anti-PD-1 monoclonal antibodies (32D6) in immunotherapy for therapeutic purposes that produced the expected results. CONCLUSIONS: This method can be used to facilitate an increased throughput of the entire process from multiplex immunization to acquisition of functional rat monoclonal antibodies and facilitate their expression and feasibility using a single plasmid.