No abstract

Dendritic cells (DCs) are the most potent antigens presenting cells in the immune system. They have a high capacity to trigger antigen-specific immune responses and promote both adaptive immunity and innate immunity. In the past decade, DC vaccine has been introduced as a new therapeutic strategy in cancer patients. DC-based immunotherapy is safe and can promote antitumor immune responses and prolonged survival of cancer patients. However, the current approaches of DC vaccination are far from optimal efficacy in advanced cancers. In this paper, we present recent findings about DC vaccine, its clinical application and efficacy in various cancers, as well as improved approaches in the preparation of DC vaccine.

Surgery, chemotherapy, and radiotherapy are successfully used to treat patients with tumors or cancers. However, the innovation of more potent therapeutic modalities is essential for the efficient treatment of patients with advanced cancers. More than two centuries ago, bacteria have been observed to have beneficial effects in some cancer patients. Virulence factors of some bacteria and their infectious behavior in the body suggest their effectiveness in tumor suppression. At present, bacillus calmette-guérin (BCG), a live attenuated strain of Mycobacterium bovis, is currently used to treat bladder cancer. Some other bacteria have also been found to have antitumor activities. Anaerobic bacteria can colonize solid tumors and exert an intrinsic antitumor effect. Salmonella is the most studied bacterium in the field of bacterial anticancer therapy in preclinical studies. In this article, we discuss progress in the development of bacterial anticancer vaccines, especially Salmonella-based vaccines, their antitumor efficacy, and mechanisms involved in vaccine-mediated cancer cell death.

Background: Dendritic cell (DC) vaccine is a hopeful approach for cancer treatment. In clinical trials, DC vaccines have produced clinical responses in some cancer patients. However, DC vaccines efficacy is not satisfactory in most types of cancer and more efforts must be done to improve their effectiveness in advanced cancers. Understanding the influence of tumor cells and tumor stromal cells on DCs and the antitumor activity of ex vivo generated DCs in the tumor microenvironment can help to augment antitumor efficiency of ex vivo generated DCs. In a fibrosarcoma tumor model, we explored effects of the tumor microenvironment on the antitumor efficacy of ex vivo generated DCs. Methods: DCs were generated from mouse bone marrow precursor cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with tumor antigens and matured in the presence of tumor necrosis factor-alpha (TNF-α), lipopolysaccharide (LPS), or TNF-α plus LPS. Mature or immature DCs were injected subcutaneously before tumor inoculation or were directly injected into the tumor tissue. Results: Tumor antigen-pulsed DCs matured in the presence of TNF-α plus LPS showed appropriate functionality in vitro, including IL-12 secretion and induction of lymphocyte proliferation. Tumor lysate-loaded DCs matured in the presence of TNF-α did not show appropriate antitumor function in vivo. Injection of antigen-unpulsed mature DCs two days before tumor inoculation resulted in antitumor effects. In contrast, injection of immature DCs directly into the tumor tissue enhanced the tumor growth. Conclusion: These results suggest that tumor cells, tumor stromal cells, or tumor derived factors can influence DCs to have tumor-promoting function. Appropriate maturation induction in ex vivo generated DCs and manipulating the tumor microenvironment before DC vaccination may improve antitumor activity of DC vaccines in cancer patients.

Virotherapy with oncolytic viruses that preferentially infect and kill cancer cells is a novel and promising strategy for cancer treatment. Newcastle disease virus (NDV), which is pathogenic in birds, has beneficial clinical effects in cancer patients. NDV virotherapy is safe and elicits an antitumor response in patients affected by different types of cancers. The selective replication of NDV in tumor cells, the lack of genetic recombination, the lack of interaction with host cell DNA, and safety of NDV vaccination in cancer patients has resulted in NDV virotherapy to be accepted as a potentially attractive anticancer modality. However, more knowledge is needed to support the development of optimal NDV-based treatment modality for cancer. In this paper, the biological characteristics of NDV, the clinical effectiveness of NDV-based anticancer vaccination, immunobiology of NDV virotherapy in cancer patients, immune responses to NDV vaccines, and NDV-induced immunogenic cell death and apoptosis of cancer cells have been discussed in detail.