scholarly journals DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine MEDI0457

2020 ◽  
Author(s):  
2001 ◽  
Vol 12 (17) ◽  
pp. 2065-2079 ◽  
Author(s):  
Yueh-Lun Lee ◽  
Yi-Ling Ye ◽  
Chun-I Yu ◽  
Ya-Ling Wu ◽  
Yih-Loong Lai ◽  
...  

2002 ◽  
Vol 36 ◽  
pp. 224
Author(s):  
Hanns Loehr ◽  
Benedikt Bubl ◽  
Wulf Boecher ◽  
Sabine Herzog-Hauff ◽  
Martin Hoffstedt ◽  
...  

2008 ◽  
Vol 15 (8) ◽  
pp. 1229-1237 ◽  
Author(s):  
Evelyn Guirado ◽  
Olga Gil ◽  
Neus Cáceres ◽  
Mahavir Singh ◽  
Cristina Vilaplana ◽  
...  

ABSTRACT RUTI is a therapeutic vaccine that is generated from detoxified and liposomed Mycobacterium tuberculosis cell fragments that has demonstrated its efficacy in the control of bacillus reactivation after short-term chemotherapy. The aim of this study was to characterize the cellular immune response generated after the therapeutic administration of RUTI and to corroborate the lack of toxicity of the vaccine. Mouse and guinea pig experimental models were infected with a low-dose M. tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in both experimental models. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mouse and guinea pig models. This was not the case after Mycobacterium bovis BCG treatment. Cellular immunity was studied through the characterization of the intracellular gamma interferon (IFN-γ)-producing cells after the splenocytes' stimulation with M. tuberculosis-specific structural and growth-related antigens. Our data show that the difference between the therapeutic administration of BCG and RUTI resides mainly in the stronger activation of IFN-γ + CD4+ cells and CD8+ cells against tuberculin purified protein derivative, ESAT-6, and Ag85B that RUTI generates. Both vaccines also triggered a specific immune response against the M. tuberculosis structural antigens Ag16kDa and Ag38kDa and a marked mRNA expression of IFN-γ, tumor necrosis factor, interleukin-12, inducible nitric oxide synthase, and RANTES in the lung. The results show that RUTI's therapeutic effect is linked not only to the induction of a Th1 response but also to the stimulation of a quicker and stronger specific immunity against structural and growth-related antigens that reduces both the bacillary load and the pulmonary pathology.


2020 ◽  
Vol 8 (1) ◽  
pp. e000612 ◽  
Author(s):  
Claire Smalley Rumfield ◽  
Samuel T Pellom ◽  
Y Maurice Morillon II ◽  
Jeffrey Schlom ◽  
Caroline Jochems

BackgroundWhile prophylactic human papillomavirus (HPV) vaccines will certainly reduce the incidence of HPV-associated cancers, these malignancies remain a major health issue. PDS0101 is a liposomal-based HPV therapeutic vaccine consisting of the immune activating cationic lipid R-DOTAP and HLA-unrestricted HPV16 peptides that has shown in vivo CD8+ T cell induction and safety in a phase I study. In this report, we have employed the PDS0101 vaccine with two immune modulators previously characterized in preclinical studies and which are currently in phase II clinical trials. Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domains of the transforming growth factor-β receptor type II (TGFβRII) fused to a human IgG1 monoclonal antibody blocking programmed cell death protein-1 ligand (PDL1), designed both as a checkpoint inhibitor and to bring the TGFβRII ‘trap’ to the tumor microenvironment (TME). NHS-interleukin-12 (NHS-IL12) is a tumor targeting immunocytokine designed to bring IL-12 to the TME and thus enhance the inflammatory Th1 response.MethodsWe employed TC-1 carcinoma (expressing HPV16 E6 and E7 and devoid of PDL1 expression) in a syngeneic mouse model in monotherapy and combination therapy studies to analyze antitumor effects and changes in immune cell types in the spleen and the TME.ResultsAs a monotherapy, the PDS0101 vaccine generated HPV-specific T cells and antitumor activity in mice bearing HPV-expressing mEER oropharyngeal and TC-1 lung carcinomas. When used as a monotherapy in the TC-1 model, NHS-IL12 elicited antitumor effects as well as an increase in CD8+ T cells in the TME. When used as a monotherapy, bintrafusp alfa did not elicit antitumor effects or any increase in T cells in the TME. When all three agents were used in combination, maximum antitumor effects were observed, which correlated with increases in T cells and T-cell clonality in the TME.ConclusionThese studies provide the rationale for the potential clinical use of combinations of agents that can (1) induce tumor-associated T-cell responses, (2) potentiate immune responses in the TME and (3) reduce immunosuppressive entities in the TME.


2021 ◽  
Author(s):  
Sahar Sadr-Momtaz ◽  
Maryam Aftabi ◽  
Emad Behboudi ◽  
Malihe Naderi ◽  
Anahita Hashemzadeh-Omran ◽  
...  

Abstract Introduction: In humans, approximately 5% of all cancers are attributable to HPV infection. Prophylactic vaccines can inhibit viral migration and persistence. However, requirement to develop therapeutic treatments prevails. To achieve this goal, we designed a therapeutic HPV DNA vaccine encoding a construct of E6/E7/L1 and used NSP4 antigen as adjuvant to assess efficiency of this construct in generating antigen-specific antitumor immune responses.Material and Methods: Sixty female C57BL/6 mice (6–8 weeks old) were purchased from Institute Pasteur of Iran. 30 of them became cancerous, but 30 of them were healthy control. To amplify E6/E7/L1-pcDNA3, NSP4-pcDNA3, expression vector of DH5α and TC-1 cell line were used to generate a tumor. Mice were immunized with HPV DNA vaccine. Cell proliferation was assessed by MTT assay. Finally, we assessed cytokine responses (IL-2, IL-4, INF- γ), in the serum of mice spleen cells.Result: Mice receiving the NSP4/E6-E7-L1 vaccine had the highest stimulatory index compared to other groups but it was not significant. Interleukin 4/12 and INF-γ production were significantly higher in E6-E7-L1 / NSP4 group and E6-E7-L1 group compared to other groups (P <0.05). Among different groups, E6/E7/L1 + NSP4 group was able to slow down the tumor growth process, but it was not significant (p>0.05). Among the cytokines mentioned, IFN-γ and IL-12 are among the cytokines that stimulate the Th1 pathway and IL-4 cytokine stimulates the Th2 pathway and B lymphocytes.Conclusion: Our data suggest that present vaccine can stimulate innate and acquired immunity response, and can be a therapeutic vaccine in the tumoric mice.


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