Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo

Lu, Yue; Mekoo, Didier J L; Ouyang, Kang; Hu, Xiangbing; Liu, Yanhua; Lin, Min; Jin, Liang; Cao, Ruihua; Li, Taiming; Zhang, Yankai; Fan, Huiying; Liu, Jingjing

doi:10.1677/erc-09-0058

Cited by 12 publications

(10 citation statements)

References 39 publications

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“…Furthermore, the capacity of M2 in enhancing the maturation of DCs and improving the antitumor effects of H-D was higher than the introduction of one (M) or 3mHSP70 407-426 (M3). Surprisingly, the result was conformity with the achievement which was first employing M2 to improve the immunogenicity of self-epitope vaccines in our lab [26,27]. We supposed M2 may strengthen the interaction between DCs and T cells and assist H22 cell lysate to activate the naïve T cells and then induce more potent T cell response than M or M3 against HCC.…”

Section: Discussionsupporting

confidence: 82%

Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

Xing

Wang

et al. 2011

International Immunopharmacology

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Section: Discussionsupporting

confidence: 82%

Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

Xing

Wang

et al. 2011

International Immunopharmacology

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“…Peptide P10 was included in our protocol to act similarly to the Pan HLA DR‐binding Epitope (PADRE). 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%

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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“…[19][20][21] Herein, M 2 was introduced to conjugate with glutaraldehyde-fixed HUVEC to prepare a HUVEC-M 2 vaccine, which was expected to have an enhanced antitumor effect. The 3 major findings of this study supported our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

A Fixed Human Umbilical Vein Endothelial Cell Vaccine With 2 Tandem Repeats of Microbial HSP70 Peptide Epitope 407-426 As Adjuvant for Therapy of Hepatoma in Mice

Xu¹,

Zhou²,

Xie³

et al. 2015

Journal of Immunotherapy

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Various studies have indicated that vaccination with endothelial cells targeting tumor angiogenesis is an effective approach for inhibiting tumor growth and metastasis. However, our previous study about a viable human umbilical vein endothelial cell (HUVEC) vaccine demonstrated that the antitumor efficiency of the targeted therapy using HUVEC plus appropriate adjuvant is feasible but need further optimization. In this study, glutaraldehyde-fixed HUVEC, tested as another antigen form, was conjugated with 2 repeats of mycobacterial HSP70(407-426) (M2) to prepare a novel HUVEC-M2 vaccine, which was expected to have an enhanced antitumor efficacy. HUVEC-M2 was administrated in mice by subcutaneous immunization in both prophylactic and therapeutic procedures. Compared with HUVEC alone, HUVEC-M2 induced a more significant inhibition on the growth of H22 hepatocellular carcinoma in mice and prolonged the survival of H22 hepatocellular carcinoma-bearing mice in both prophylactic and therapeutic procedures. Meanwhile, specific CTLs as well as antibodies against tumor endothelium correlated well with the inhibition effect were evoked by HUVEC-M2, which indicated that antiangiogenesis was mainly responsible for the antitumor effect. Moreover, the attenuated tumor-induced angiogenesis in intradermal tumor model and reduced vessel density of the intradermal tumor in mice further confirmed the antiangiogenesis effect elicited by HUVEC-M2. All the data suggested that M2 could be used as a potent adjuvant to conjugate with glutaraldehyde-fixed HUVEC for preparing HUVEC vaccines and would have important clinical implications for adjuvant cancer therapy.

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Strong humoral response elicited by a DNA vaccine targeting gastrin-releasing peptide with optimized adjuvants inhibits murine prostate carcinoma growth in vivo

Cited by 12 publications

References 39 publications

Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407–426 and OK-432

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

A Fixed Human Umbilical Vein Endothelial Cell Vaccine With 2 Tandem Repeats of Microbial HSP70 Peptide Epitope 407-426 As Adjuvant for Therapy of Hepatoma in Mice

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