987 DNA encoding a Pan-MHC class II peptide analogue augmented antigen-specific cellular immunity and suppressive effects on tumor growth elicited by DNA vaccine immunotherapy

Teramoto, K.; Kontani, Keiichi; Ozaki, Yoshitomo; Kudoh, Shoji; Sawai, Satoru; Tezuka, Noriaki; Fujino, Shozo; Itoh, Yoshikiyo; Ogasawara, K.

doi:10.1016/s1359-6349(03)91014-7

Cited by 7 publications

(9 citation statements)

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“…The PADRE peptides are used as immunomodulators for stimulating immune responses in several models where T CD4 + cell help was critical 50 , 51 , 52 , 53 . Heterologous MHC‐II‐binding peptides, which were not originated from the tumor, were previously used successfully to induce a protective response in experimental tumor models, including B16 melanoma 17 , 18 , 19 …”

Section: Discussionmentioning

confidence: 99%

“…Although major histocompatibility complex (MHC) class II‐binding tumor‐specific peptides are necessary for induction of tumor‐specific CD4 + T cells, 16 there are examples of heterologous MHC II‐binding peptides that are powerful immunomodulating agents, stimulating the anti‐tumor cytolytic activity of tumor‐specific CD8 + T lymphocytes and increasing survival of tumor‐bearing animals in experimental models. Sources of those peptides were diverse and included ovalbumin, 17 microbial 18 and respiratory chain proteins 19 . In common, all these heterologous immunomodulatory peptides bind to a broad range of MHC class II molecules and induce protective anti‐tumor responses.…”

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confidence: 99%

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Anti‐metastatic immunotherapy based on mucosal administration of flagellin and immunomodulatory P10

et al. 2014

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Current therapies against malignant melanoma generally fail to increase survival in most patients, and immunotherapy is a promising approach as it could reduce the dosage of toxic therapeutic drugs. In the present study, we show that an immunotherapeutic approach based on the use of the Toll-like receptor (TLR)-5 ligand flagellin (Salmonella Typhimurium FliCi) combined with the major histocompatibility complex class II-restricted P10 peptide, derived from the Paracoccidioides brasiliensis gp43 major surface protein, reduced the number of lung metastasis in a murine melanoma model. Compounds were administered intranasally into C57Bl/6 mice intravenously challenged with syngeneic B16F10-Nex2 melanoma cells, aiming at the local (pulmonary) immune response modulation. Along with a marked reduction in the number of lung nodules, a significant increase in survival was observed. The immunization regimen induced both local and systemic proinflammatory responses. Lung macrophages were polarized towards a M1 phenotype, lymph node cells, and splenocytes secreted higher interleukin-12p40 and interferon (IFN)-γ levels when re-stimulated with tumor antigens. The protective effect of the FliCi+P10 formulation required TLR-5, myeloid differentiation primary response gene 88 and IFN-γ expression, but caspase-1 knockout mice were only partially protected, suggesting that intracellular flagellin receptors are not involved with the anti-tumor effect. The immune therapy resulted in the activation of tumor-specific CD4 + T lymphocytes, which conferred protection to metastatic melanoma growth after adoptive transfer. Taken together, our results report a new immunotherapeutic approach based on TLR-5 activation and IFN-γ production capable to control the metastatic growth of B16F10-Nex2 melanoma, being a promising alternative to be associated with chemotherapeutic drugs for an effective anti-tumor responses.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Anti‐metastatic immunotherapy based on mucosal administration of flagellin and immunomodulatory P10

et al. 2014

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“…In addition, to evaluate humoral immunity elicited in mice given TGFR DNA, the level of anti-OVA antibody in sera was examined by ELISA as described previously (28). The level of anti-OVA antibody was elevated in the sera from mice given TGFR DNA but not Mock DNA (P = 0.004) or PBS (P = 0.003; Fig.…”

Section: Cd8mentioning

confidence: 99%

“…To evaluate the cytotoxic activity of spleen cells, cells were subjected to the 51 Cr-release assay targeting E.G7 as described previously (28). Potent cytotoxic activity against E.G7 was elicited in spleen from mice given TGFR DNA compared with Mock DNA (P = 0.005) or PBS (P = 0.00002; Fig.…”

Section: Cd8mentioning

confidence: 99%

Inhibition of Transforming Growth Factor-β–Mediated Immunosuppression in Tumor-Draining Lymph Nodes Augments Antitumor Responses by Various Immunologic Cell Types

Fujita¹,

Teramoto²,

Ozaki³

et al. 2009

Cancer Research

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Tumor-draining lymph nodes (DLN) are the most important priming sites for generation of antitumor immune responses. They are also the location where an immunosuppressive cytokine, transforming growth factor-β (TGF-β), plays a critical role in suppressing these antitumor immune responses. We focused on TGF-β-mediated immunosuppression in DLNs and examined whether local inhibition of TGF-β augmented antitumor immune responses systemically in tumor-bearing mice models. For inhibition of TGF-β-mediated immunosuppression in DLNs, C57BL/6 mice subcutaneously bearing E.G7 tumors were administered plasmid DNA encoding the extracellular domain of TGF-β type II receptor fused to the human IgG heavy chain (TGFR DNA) i.m. near the established tumor. In DLNs, inhibition of TGF-β suppressed the proliferation of regulatory T cells and increased the number of tumor antigenspecific CD4 + or CD8 + cells producing IFN-γ. Enhancement of antitumor immune responses in DLNs were associated with augmented tumor antigen-specific cytotoxic and natural killer activity in spleen as well as elevated levels of tumor-specific antibody in sera. The growth of the established metastatic as well as primary tumors was effectively suppressed via augmented antitumor immune responses. Inhibition of TGF-β-mediated immunosuppression in DLNs is significantly associated with augmented antitumor responses by various immunocompetent cell types. This animal model pro-vides a novel rationale for molecular cancer therapeutics targeting TGF-β. [Cancer Res 2009;69(12):5142-50]

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“…DNA vaccination enables maintenance of tumor antigen expression at the vaccination site and results in immune responses in the host, therefore, shedding light on the treatment of cancer. It has been reported that tumor growth is suppressed when tumor cells are implanted in mice previously immunized with DNA vaccines encoding tumor antigens [22-25]. …”

Section: Discussionmentioning

confidence: 99%

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Ren

Chen

et al. 2004

J Transl Med

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BackgroundProstate-specific membrane antigen (PSMA) is a well characterized prostate-specific tumor associated antigen. Its expression is elevated in prostate carcinoma, particularly in metastatic and recurrent lesions. These observations suggest that PSMA can be used as immune target to induce tumor cell-specific recognition by the host and, consequently tumor rejection. We utilized a DNA-based vaccine to specifically enhance PSMA expression. An immune modulator, such as CpG oligodeoxynucleotides which promote Th1-type immune responses was combined to increase the efficacy of tumor recognition and elimination.MethodsA eukaryotic expression plasmid pCDNA3.1-PSMA encoding full-length PSMA was constructed. C57BL/6 mice were immunized with endotoxin-free pCDNA3.1-PSMA alone or in combination with CpG oligodeoxynucleotides by intramuscular injection. After 4 immunizations, PSMA specific antibodies and cytotoxic T lymphocyte reactivity were measured. Immunized C57BL/6 mice were also challenged subcutaneously with B16 cells transfected with PSMA to evaluate suppression of tumor growth.ResultsVaccine-specific cytotoxic T lymphocytes reactive with B16 cells expressing PSMA could be induced with this treatment schedule. Immune protection was observed in vaccinated mice as indicated by increased tumor growth in the control group (100%) compared with the groups vaccinated with DNA alone (66.7%) or DNA plus CpG oligodeoxynucleotides (50%) respectively. Average tumor volume was smaller in vaccinated groups and tumor-free survival time was prolonged by the vaccination.ConclusionThe current findings suggest that specific anti-tumor immune response can be induced by DNA vaccines expressing PSMA. In addition, the suppression of in vivo growth of tumor cells expressing PSMA was augmented by CpG oligodeoxynucleotides. This strategy may provide a new venue for the treatment of carcinoma of prostate after failure of standard therapy.

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987 DNA encoding a Pan-MHC class II peptide analogue augmented antigen-specific cellular immunity and suppressive effects on tumor growth elicited by DNA vaccine immunotherapy

Cited by 7 publications

References 0 publications

Anti‐metastatic immunotherapy based on mucosal administration of flagellin and immunomodulatory P10

Anti‐metastatic immunotherapy based on mucosal administration of flagellin and immunomodulatory P10

Inhibition of Transforming Growth Factor-β–Mediated Immunosuppression in Tumor-Draining Lymph Nodes Augments Antitumor Responses by Various Immunologic Cell Types

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