Expression of soluble TGF-β receptor II by recombinant Vaccinia virus enhances E7 specific immunotherapy of HPV16 tumors

Zurkova, Kamila; Chlanda, Petr; Samkova, Z; Babiarova, Katarina; Kutinovà, L; Kryštofová, Jitka; Hainz, Petr; Němečková, Šárka

doi:10.4149/neo_2011_03_181

Cited by 4 publications

(1 citation statement)

References 36 publications

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“…11 On the other hand, we have already prepared several rVACVs where a too high expression of a protein was incompatible with the formation of an infectious virus and where the expression under the H5 promoter gave higher yields of the transgenic product, as was the case of the P13-TbRII viruses. 61 Toxicity of high levels of IGFBP-3 (under sE/L promoter) can be connected with induction of apoptosis that, in vaccination strain Praha, is not fully inhibited by antiapoptotic mechanisms as in other VACV strains (for example, WR strain). 62 Second, the analysis of immunogenicity revealed that both P13-SigE7Lamp-H5-IGFBP-3 and P13-SigE7Lamp-E/L-IGFBP-3 elicited higher anti-VACV responses than P13-SigE7Lamp-TK À , although not statistically significantly because of the high variability.…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity and immunogenicity of recombinant vaccinia virus expressing HPV 16 E7 protein SigE7LAMP is enhanced by high-level coexpression of IGFBP-3

et al. 2014

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We constructed recombinant vaccinia viruses (VACVs) coexpressing the insulin-like growth factor-binding protein-3 (IGFBP-3) gene and the fusion gene encoding the SigE7Lamp antigen. The expression of the IGFBP-3 transgene was regulated either by the early H5 promoter or by the synthetic early/late (E/L) promoter. We have shown that IGFBP-3 expression regulated by the H5 promoter yielded higher amount of IGFBP-3 protein when compared with the E/L promoter. The immunization with P13-SigE7Lamp-H5-IGFBP-3 virus was more effective in inhibiting the growth of TC-1 tumors in mice and elicited higher T-cell response against VACV-encoded antigen than the P13-SigE7Lamp-TK(-) control virus. We found that high-level production of IGFBP-3 enhanced virus replication both in vitro and in vivo, resulting in more profound antigen stimulation. Production of IGFBP-3 was associated with a higher adsorption rate of P13-SigE7Lamp-H5-IGFBP-3 to CV-1 cells when compared with P13-SigE7Lamp-TK(-). Intracellular mature virions (IMVs) of the IGFBP-3-expressing virus P13-SigE7Lamp-H5-IGFBP-3 have two structural differences: they incorporate the IGFBP-3 protein and they have elevated phosphatidylserine (PS) exposure on outer membrane that could result in increased uptake of IMVs by macropinocytosis. The IMV PS content was measured by flow cytometry using microbeads covered with immobilized purified VACV virions.

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Section: Discussionmentioning

confidence: 99%

Antitumor activity and immunogenicity of recombinant vaccinia virus expressing HPV 16 E7 protein SigE7LAMP is enhanced by high-level coexpression of IGFBP-3

et al. 2014

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Reprogramming the tumor microenvironment to enhance adoptive cellular therapy

Beavis

Slaney

Kershaw

et al. 2016

Seminars in Immunology

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HPV-Specific Immunotherapy: Key Role for Immunomodulators

Wall¹,

Nijman²,

Daemen

2014

ACAMC

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Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic.

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Expression of soluble TGF-β receptor II by recombinant Vaccinia virus enhances E7 specific immunotherapy of HPV16 tumors

Cited by 4 publications

References 36 publications

Antitumor activity and immunogenicity of recombinant vaccinia virus expressing HPV 16 E7 protein SigE7LAMP is enhanced by high-level coexpression of IGFBP-3

Antitumor activity and immunogenicity of recombinant vaccinia virus expressing HPV 16 E7 protein SigE7LAMP is enhanced by high-level coexpression of IGFBP-3

Reprogramming the tumor microenvironment to enhance adoptive cellular therapy

HPV-Specific Immunotherapy: Key Role for Immunomodulators

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