Therapeutic tumor vaccines-a rising star to benefit cancer patients

Malignant tumors are still a worldwide threat to human health.Tumor treatment strategies are constantly evolving,and the advent of tumor immunotherapy has brought up hope to many types of tumors,especially for those that are refractory to conventional therapies including surgery,radiotherapy,and chemotherapy.Tumor vaccines can initiate or amplify an anti-tumor immune response in tumor patients through active immunization,and therefore occupy an important position in tumor immunotherapy.The main types of tumor vaccines include tumor cell vaccines,dendritic cell vaccines,polypeptide vaccines and nucleic acid vaccines.Due to factors such as poor antigen selection and suppressive tumor microenvironment,earliest tumor vaccines on clinical trials failed to achieve satisfactory clinical effects.However,with the development of second-generation genome sequencing technologies and bioinformatics tools,it is possible to predict neoantigens generated by tumor-specific mutations and therefore prepare personalized vaccines.This article summarizes the global efforts in developing tumor vaccines and highlights several representative tumor vaccines in each category.

Immunotherapeutic effects of dendiritic cells vaccine pulsed with tumor cell lysate in mice with pancreatic carcinoma

Objective To observe the immunotherapeutic effects of dendritic cells vaccine pulsed with tumor cell lystate on mice with pancreatic carcinoma. Methods Dendritic cells (MTSC4) were pulsed with tumor cells lysate. The immune preventative and immnotherapeutic effects of DC vaccines on mice with pancreatic carcinoma were assessed. Results After vaccination of the DC vaccines,mice remained tumor-free for at least 25 days in DCs vaccines group,but in other groups the subcutaneous implantation tumorigenesis were found beginning 3 to 9 days. CTL stimulated by DC vaccines effected cytolytic activity against pancreatic carcinoma cells. The survival period was obviously prolonged in DCs vaccines group (56 ±9)d than in other groups P【0.01) and tumors (1.4 ±0.8)g in DCs vaccines group were significantly smaller than that in other groups (P 【 0. 05). Conclusion Tumor cell lysate-pulsed dendrtic cells vaccines can induce a specific and effective immune response against pancreatic carcinoma cell implanted in mice.

Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine

Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials.However,the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored.Here,we demonstrate that oxidized mitochondrial DNA(mtDNA)and stimulator of interferon genes(STING)signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine.Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells.Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells(DCs).Oxidized mtDNA,as a DAMP or adjuvant,activated the STING-TBK1-IRF3-IFN-β pathway in DCs,which subsequently cross-presented irradiated tumor cell-derived antigens to CD8^(+)T cells and elicited antitumor immunity.The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity,which may have implications for new strategies to improve the efficacy of irradiated vaccines.

Induction of T-cell immunity against leukemia by dendritic cells pulsed with total RNA isolated from leukemia cells

Objectives To assess the feasibility and efficacy of eliciting leukemia-specific T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells (DCs) pulsed with total RNA from leukemia cells.Methods DCs generated from bone marrow culture in vitro in the presence of combined cytokines were pulsed with cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune protection and proghosis of mice with leukemia were studied.Results DCs pulsed with total RNA isolated from cultured L615 cells (DCs/RNA) were remarkably effective in stimulating L615-specific T-cell response in vitro, but did not cross-react with other leukemia cells from syngeneic mice. Vaccination of naive mice with viable DCs/RNA vaccine was able to partly protect from challenge with a lethal dose of live L615 cells, leading to low leukemia incidence and overall survival prolongation. Statistically significant survival was also observed in a low lethal dose of L615-bearing mice that received treatment using viable DCs / RNA vaccine alone, suggesting that systemic administration of IL-2 could enhance the anti-tumor efficacy of leukemia RNA/DCs vaccine.Conclusions These data support the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia immunity against unidentified leukemia-associated antigens for treatment of leukemia-bearing animals.