• IMMUNE NETWORK
• /
• v.5 no.2
• /
• pp.55-67
• /
• 2005

Cancer vaccine is an active immunotherapy to stimulate the immune system to mount a response against the tumor specific antigen. Working as a stimulant to the body's own immune system, cancer vaccines help the body recognize and destroy targeted cancers and may help to shrink advanced tumors. Research is currently underway to develop therapeutic cancer vaccines. It is also possible to develop prophylactic vaccines in the future. The whole cell approach to eradicate cancer has used whole cancer cells to make vaccine. In an early stage of this approach, whole cell lysate or a mixture of immunoadjuvant and inactivated cancer cells has been used. Improved vaccines are being developed that utilize cytokines or costimulatory molecules to mount an attack against cancer cells. In case of melanoma, these vaccines are expected to have a therapeutic effect of vaccine. Furthermore, it is attempting to treat stomach cancer, colorectal cancer, pancreatic cancer, and prostate cancer. Other vaccines are being developing that are peptide vaccine, recombinant vaccine and dendritic cell vaccine. Out of them, reintroduction of antigen-specific dendritic cells into patient and DNA vaccine are mostly being conducted. Currently, research and development efforts are underway to develop therapeutic cancer vaccine such as DNA vaccine for the treatment of multiple forms of cancers.

• IMMUNE NETWORK
• /
• v.10 no.6
• /
• pp.206-211
• /
• 2010

Background: Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of colon cancer because it has been recurred and produced few side effects in patients. Secretory glycoprotein 90K has been found at elevated level in various cancer tissues and sera. We investigated to establish a more effective DC vaccine for the treatment of colon cancer in which the levels of 90K are elevated. Methods: We obtained the concentrated 90K from 293T cells stably expressing 90K. DCs were cultured from peripheral blood monocytes, and a DC vaccine pulsed with tumor lysate was compared with a DC vaccine pulsed with 90K. We measured the functional activity for CTLs by using IFN-${\gamma}$-enzyme linked immunoabsorbent spot (ELISPOT) assay. Results: DCs pulsed with tumor lysate+90K exhibited the enhanced T cell stimulation, polarization of $\ddot{i}$ T cell toward Th1. The CTLs generated by DCs pulsed with 90K efficiently lysed HCT116 cells. The results indicate that 90K-speicifc-CTLs can recognize 90K proteins naturally presented by colon cancer cells. Conclusion: Our study suggests that 90K-specific CTLs generated by 90K-pulsed DCs could be useful effector cells for immunotherapy in colon cancer.

• Parasites, Hosts and Diseases
• /
• v.58 no.2
• /
• pp.185-189
• /
• 2020

Immunogenicity of dendritic cell-derived exosomes stimulated with Toxoplasma gondii lysates (TLA exo), mixed with cholera toxin as an adjuvant, was investigated in mice immunized via 2 mucosal routes (ocular vs intranasal). BALB/c mice were injected 3 times with TLA exo vaccine at 2 week interval, and the levels of IgG in serum and IgA in tear, saliva, feces, and vaginal wash were measured. To observe the expression of T. gondii-specific B1 gene, mice infected with ME49 T. gondii cysts were immunized with TLA exo or PBS exo (not stimulated with TLA), and their brain tissues were examined. The mice vaccinated via intranasal route elicited significantly higher humoral and mucosal immune responses compared with mice treated with PBS alone. Also, mice immunized via ocular route (by eyedrop) induced significantly higher T. gondii-specific IgG in serum and IgA in tear and feces in comparison with PBS controls. B1 gene expression was significantly lower in TLA exo vaccinated mice than in PBS or PBS exo vaccinated mice. These results demonstrated that ocular immunization of mice with TLA exo vaccine has the potential to stimulate systemic or local antibody responses. This study also highlighted an advantage of an eyedrop vaccine as an alternative for T. gondii intranasal vaccines.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3109-3116
• /
• 2013

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

• IMMUNE NETWORK
• /
• v.10 no.1
• /
• pp.5-14
• /
• 2010

Background: There have been several reports describing the capability of ginseng extracts as an adjuvant. In this study, we tested if ginsan, a polysaccharide extracted from Panax ginseng, was effective in enhancing antibody response to orally delivered Salmonella antigen. Methods: Ginsan was treated before oral salmonella antigen administration. Salmonella specific antibody was determined by ELISA. mRNA expression was determined by RT-PCR. Cell migration was determined by confocal microscopy and flow cytometry. COX expression was detected by western blot. Results: Ginsan treatment before oral Salmonella antigen delivery significantly increased both secretory and serum antibody production. Ginsan increased the expression of COX in the Peyer's patches. Various genes were screened and we found that CCL3 mRNA expression was increased in the Peyer's patch. Ginsan increased dendritic cells in the Peyer's patch and newly migrated dendritic cells were mostly found in the subepithelial dome region. When COX inhibitors were treated, the expression of CCL3 was reduced. COX inhibitor also antagonized both the migration of dendritic cells and the humoral immune response against oral Salmonella antigen. Conclusion: Ginsan effectively enhances the humoral immune response to orally delivered antigen, mediated by CCL3 via COX. Ginsan may serve as a potent vaccine suppliment for oral immunization.

• Proceedings of the PSK Conference
• /
• 2001.10a
• /
• pp.200.1-200.1
• /
• 2001

• BMB Reports
• /
• v.49 no.10
• /
• pp.554-559
• /
• 2016

Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigen-presenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes ᴅ-alanyl-ᴅ-alanine dipeptidase, which catalyzes the hydrolysis of ᴅ-alanyl-ᴅ-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2447-2451
• /
• 2014

Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.3
• /
• pp.489-499
• /
• 2019

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCNs to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic $CD8^+$ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and $CD8^+$ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.1
• /
• pp.38-48
• /
• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.