BACKGROUND: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-alpha or lamivudine. However, interferon-alpha is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. METHODS: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb/c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. RESULTS: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. CONCLUSION: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.
Animals ; Carcinoma, Hepatocellular ; DNA* ; Fibrosis ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Immunoglobulin G ; Immunotherapy, Active ; Interferon-alpha ; Interleukin-12 ; Lamivudine ; Mice ; United Nations ; Vaccination ; Vaccines

Since spontaneous regression of metastatic renal cell carcinoma (mRCC) has been reported, immunotherapy for mRCC has been the therapeutic option. The goal of modulating an immune response to the tumor cell with passive and/or active immunotherapy can be achieved through the increasing technological sophistication and the understanding of the immune system. Currently, among the several available cytokines to treat mRCC, high-dose interleukin-2 (IL-2) administration is the only way to obtain complete remission. However, due to the lack of prominent benefit and toxicity of high dose IL-2 therapy, cytokine-based immunotherapy for the treatment of mRCC is threatened by the intriguing molecularly targeted agents, which are still under the trials. Different types of cellular (autologous tumor cell, gene modified tumor cell, dendritic cell) and non-cellular therapeutic vaccines of mRCC have been applied in the clinical setting, and the success of clinical effectiveness in selected population has been reported. Future treatment approaches for mRCC or locally advanced RCC would be directed with combined therapy with immunotherapy and targeted agent. Additionally, molecularly targeted agents and vaccines modulating tumor immunology cascade will be another immunotherapeutic approach for RCC.
Carcinoma, Renal Cell ; Cytokines ; Dendritic Cells ; Immune System ; Immunotherapy ; Immunotherapy, Active ; Interleukin-2 ; Vaccines

The prognosis of patients with malignant brain tumors has improved only slightly despite the combined use of surgery, radiation therapy, and chemotherapy. Immunotherapy offers some possibilities and hopes as a fourth modality for the treatment of cancers although it is still in the early stages of development. It is possible to classify immunotherapy within four generally accepted modalities : 1) restorative or nonspecific immunotherapy 2) adoptive immunotherapy 3) passive immunotherapy 4) active immunotherapy. The techniques of recombinant DNA, genetic engineering, cell fusion and hybridoma production, and molecular biology will make these therapeutic approaches more successful and as the clinical applications expand the skillful cancertherapist will become increasingly familiar with these treatments and the problems associated with their use.
Allergy and Immunology* ; Brain Neoplasms* ; Brain* ; Cell Fusion ; DNA, Recombinant ; Drug Therapy ; Genetic Engineering ; Hope ; Humans ; Hybridomas ; Immunization, Passive ; Immunotherapy* ; Immunotherapy, Active ; Immunotherapy, Adoptive ; Molecular Biology ; Prognosis

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.
Cancer Vaccines* ; Colorectal Neoplasms ; Cytokines ; Dendritic Cells ; DNA ; Humans ; Immune System ; Immunotherapy ; Immunotherapy, Active ; Melanoma ; Pancreatic Neoplasms ; Prostatic Neoplasms ; Stomach Neoplasms ; Vaccines

Heat-shock protein gp96 associates with antigenic peptides derived from tumor and virus. Exogenous gp96-peptide complexes are taken up by antigen-presenting cells through interaction with its receptor CD91 on the cell surface, and cross-present antigenic peptides to MHC class I molecules by a peptide relay line in the endoplasmic reticulum for specific T-cell activation. Meanwhile, gp96 has been shown to initiate innate immune responses through interaction with toll-like receptor 2 and toll-like receptor 4. Recent studies have shown a gp96-mediated immune balance between CTL and Tregs. With the further understanding of counteracting immunosuppressive mechanisms in gp96-induced cellular immune responses, and establishment of high level production of recombinant gp96 by the yeast, gp96 appears to be a promising candidate for designing effective therapeutic vaccines against tumor and infectious diseases.
Animals ; Communicable Diseases ; therapy ; Heat-Shock Proteins ; immunology ; therapeutic use ; Humans ; Immunotherapy, Active ; methods ; Neoplasms ; therapy ; T-Lymphocytes, Regulatory ; immunology

The development of prophylactic AIDS vaccines and immunotherapeutic approaches such as therapeutic AIDS vaccines would greatly benefit from acquired experience in reproductive immunology field relating to pregnancy and infertility. Certain immune and pathological aspects of HIV infection are closely related to problems faced by obstetricians, embryologists, gynecologists, and andrologists. This review attempts to bring together the recent advances in AIDS field with progress made in the physiology and pathology of reproduction in humans. The insight gained in reproductive biology research, particularly in the area of immunotherapy of recurrent spontaneous abortions, can help to develop better strategies for the treatment and prevention of HIV infection.
AIDS Vaccines ; therapeutic use ; Abortion, Habitual ; therapy ; Female ; HIV Infections ; therapy ; Humans ; Immunotherapy, Active ; Infertility, Female ; therapy ; Pregnancy

OBJECTIVESome research has shown that Newcastle disease virus (NDV) is effective in the treatment of various tumors, including transferred melanoma and well differentiated renal cell carcinoma. This study aimed to evaluate the effect of NDV against human acute monocytic leukemia SHI-1 cells in vitro and in vivo.

METHODSIn vitro, the density and morphologic changes between wild SHI-1 cells (control) and NDV-infected SHI-1 cells were observed. MTT assay was utilized to observe the effect of NDV on the proliferation of SHI-1 cells. In vivo, the effect of NDV on the tumor inhibition was assessed using SHI-1 xenografts subcutaneously established in CD-1 nude mice. NDV was given by intra-tumor injections, and the tumor inhibition rate and toxic effects were evaluated.

RESULTSIn the control group, the SHI-1 cells were observed using an inverted microscope to be regular in morphology and intensive in distribution. In the NDV-infected group, the SHI-1 cells were irregular and sparsate, and the aggregate and fused cells were common. MTT assay showed that the proliferation of SHI-1 cells were significantly inhibited by NDV at different concentrations (P<0.01) and in a time- and concentration-dependent manner. The tumor inhibition rate in the NDV group was 84.7%, which was significantly higher than that in the control group (P<0.01). No toxic effects were observed in the nude mice.

CONCLUSIONSNDV can suppress the proliferation of human acute monocytic leukemic cells both in vitro and in vivo. The safety of NDV is reliable.

Animals ; Cell Proliferation ; Humans ; Immunotherapy, Active ; Leukemia, Monocytic, Acute ; therapy ; Mice ; Mice, Nude ; Newcastle disease virus ; physiology ; Xenograft Model Antitumor Assays

Abortion, Habitual ; therapy ; Birth Weight ; Body Height ; Body Weight ; Child Development ; Female ; Follow-Up Studies ; Humans ; Immunotherapy, Active ; Infant, Newborn ; Pregnancy

PURPOSE: Dendritic cells (DCs) are the most potent antigen- presenting cells for initiating the T cell immune response in vivo. Recent studies have shown that active immunotherapy with tumor antigen pulsed DC tumor antigen specific cytotoxic T lymphocyte (CTL) response. The aim of this study was to establish clinically compatible procedures for generating human DCs and to determine if the CEA peptide- pulsed DCs can activate the CEA specific CTL responses in vitro. METHODS: DCs were generated from the peripheral blood monocytes (PBMCs) of HLA A2+ healthy donors using GM-CSF and IL-4. Phenotypic analysis was performed using flow cytometry with FITC- or PE-conjugated Abs against CD1a, CD14, CD80, HLA-DR, CD83 and CD86. The immature DCs were pulsed with a CEA peptide (HLA A2 epitope, [YLSGANLNL]) and the tumor lysates isolated from HLA A2+ CEA positive cell line, NCI-H498, and were incubated with the autologous PBMCs in order to generate an antigen specific CTLs in vitro. After three rounds of stimulation, the presence of a CEA-specific CTL response was determined using a CEA positive cell line as the specific targets with the standard 51Cr release assay, the ELISPOT assay, and the flow cytometry using CEA peptide-MHC tetramer. RESULTS: The DCs obtained after 6 days of culture expressed high levels of CD1a, HLA-DR, and CD80, which corresponded to the immature DC phenotype. The 51Cr- release assay showed that DCs pulsed with the CEA peptide or the lysates of the CEA-positive NCI-H498 cell line could stimulate the CEA-specific CTL responses. The CTL response to DCs pulsed with the CEA peptide was also generated using the DCs pulsed with the CEA peptide. In the ELISPOT assay, the number of CEA peptide-specific, INF-gamma-secreting spots were increased in the CTLs generated by DCs pulsed with the CEA pepide and the tumor lysates. In the peptide-MHC tetramer assay, the CD8+ T cells with the receptors specific to CEA-peptide were increased by stimulation with the DCs pulsed with the CEA peptide and the tumor lysates. CONCLUSION: These findings show that the CEA peptide pulsed DCs can generate CEA specific CTL responses and antigen bearing DCs can be used as the target cells for a cytotoxicity assay. This study provides the foundations for DC-based cancer immunotherapy for CEA expressing solid tumors.
Carcinoembryonic Antigen* ; Cell Line ; Dendritic Cells* ; Enzyme-Linked Immunospot Assay ; Flow Cytometry ; Foundations ; Granulocyte-Macrophage Colony-Stimulating Factor ; HLA-DR Antigens ; Humans ; Immunotherapy ; Immunotherapy, Active ; Interleukin-4 ; Lymphocytes ; Monocytes ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Cytotoxic* ; Tissue Donors

OBJECTIVETo investigate the effects of dendritic cells (DCs) transfected with survivin gene, and to observe the effective and specific anti-tumor immunological effect induced by modified DC in vitro.

METHODSSurvivin gene was transfected to DCs with liposomes. Survivin expression could be detected both in DCs cells and in cell culture with method of Western blot. Cytokines as well as cellular surface molecule such as IL-12, TNF-alpha, CD1 alpha, CD83, MHCII, CD80 and CD86 were detected. The competence of inducing human specific cytotoxic T lymphocyte (CTLs) was also detected with MTT.

RESULTSSurvivin expression could be detected both in DCs which were transfected with survivin cDNA and in cell culture superior. The IL-12 and TNF-alpha level was (265.2 +/- 32.7), (437.1 +/- 83.5) pg/ml, and much higher in transgened DC cells than blank DC cells (P < 0.05). CD1 alpha, CD83, MHCII, CD80 and CD86 was high expressed in survivin-DC cells, however, it was low expressed in blank DC cells. The lyse rate to gastric cancer cell, colon cancer cell and bile duct cancer cell was 65%, 77%, and 85% respectively, and these were much higher than those of blank DC cells.

CONCLUSIONSDCs transfected with survivin gene could induce specific cytotoxic T lymphocytes and strikingly raised DC cell's antigen present function, and have specific CTL killing activity.

Antigens, CD ; metabolism ; Dendritic Cells ; immunology ; Gastrointestinal Neoplasms ; therapy ; Humans ; Immunotherapy, Active ; In Vitro Techniques ; Inhibitor of Apoptosis Proteins ; Interleukin-12 ; secretion ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; Transfection ; Tumor Necrosis Factor-alpha ; secretion