Testing mouse mammary tumor virus superantigen as adjuvant in cytotoxic T‐lymphocyte responses against a melanoma tumor antigen

Wirth, Susanne; Bille, Frédéric; Koenig, Sylvain; Wehrli, Nathalie; Miconnet, Isabelle; Lévy, Frédéric; Diggelmann, Heidi; Romero, Pedro; Acha‐Orbea, Hans

doi:10.1002/ijc.10237

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…20) This effect has been extensively utilized for antitumor immunotherapy. [21][22][23][24][25][26][27][28] Our previous studies showed that SAgs could produce better efficacy when combined with other methods, such as genetically introduced cytokines. [29][30][31] Therefore, we wondered if SAg activation could be utilized to potentiate HSPs' antitumor-specific immunity, and we hypothesized that SAg anchored on vaccine cells transduced with HSP gene might locally break immune tolerance and cause immune-activation around the cells.…”

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confidence: 99%

Potent antitumor effect elicited by superantigen‐linked tumor cells transduced with heat shock protein 70 gene

Huang¹,

Yu²,

Wang³

et al. 2004

Cancer Science

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Heat shock proteins (HSP) induce antitumor-specific immunity via a unique mechanism, but HSP alone fails to produce a satisfactory antitumor efficacy. We considered that the potent immune-activation of superantigen (SAg) might assist HSP to elicit a strong tumor-antigen-specific immunity. We initially prepared B16 melanoma cells linked to SAg SEA via a fusion protein with a transmembrane sequence (TM), and demonstrated that SEA thus anchored on the tumor cell surface could elicit strong antitumor immunity. We then prepared cells transduced with an inducible heat shock protein 70 (HSP70) gene, and bearing SEA-TM fusion protein on the cell surface, and used these cells as a dual-modified vaccine. In this study, either in a therapeutic setting or in a pre-immune model, the SEA-anchored vaccine or the HSP70 genemodified vaccine induced marked tumor suppression, prolonged survival, augmented lymphocyte proliferation and higher NK and CTL activity in C57BL/6 mice compared with their controls (P < < < <0.01), though they were less effective than the dual-modified vaccine. Among these vaccines, the dual-modified vaccine showed the best therapeutic efficacy in B16 melanoma-bearing mice and gave the greatest protection against wild-type B16 melanoma challenge. The results indicated that the dual-modified vaccine could induce a potent tumor-antigen-specific immune response in addition to an increase of non-specific immunity. This study offers a novel approach to bridging specific and non-specific immunity for cancer therapy. (Cancer Sci 2004; 95: 160-167)

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confidence: 99%

Potent antitumor effect elicited by superantigen‐linked tumor cells transduced with heat shock protein 70 gene

Huang¹,

Yu²,

Wang³

et al. 2004

Cancer Science

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“…This was also shown in chickens vaccinated with an inactivated avian influenza vaccine added with 20 µg of a recombinant N protein expressed in baculovirus (N-Bac), analyzing the expression of mRNA by RT/PCR (Loza-Rubio et al 2002). Recently, some reports have recognized superantigens as immunomodulators and adjuvants, and their role in protection (Papageorgiou and Acharya 1997;Okamoto et al 2001;Loza-Rubio 2003;Wirth et al 2002;McAleer et al 2007;Miles et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Nucleocapsid of rabies virus improve immune response of an inactivated avian influenza vaccine

2009

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The purpose of this study was to determine if nucleocapsid of rabies virus could improve the immune response (humoral and protective) of chickens vaccinated against avian influenza with an inactivated avian influenza experimental vaccine (AIV). On the other hand, AIV with and without NC was compared with an inactivated oil emulsion avian influenza commercial vaccine (CV) virus, currently used in Mexico. Groups of 8 day old chickens were vaccinated intracutaneously with an AIV (group 1); group 2, AIV supplemented with 20 microg of nucleocapsid of rabies virus (NC); Group 3, commercial vaccine (CV) and control groups (4 and 5) with 20 microg of NC and non-infected allantoic fluid, respectively. CV showed a better antibody-mediated response (p < 0.001) after and before challenging; which correlated with the best protection; while NC improved the protection in comparison with group 1. This is the first report on the potential utility of the rabies virus N protein to improve immune response in domestic species.

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Enhanced anti-tumor immunity by superantigen-pulsed dendritic cells

Kato

Nakamura

Suda

et al. 2011

Cancer Immunol Immunother

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Staphylococcal enterotoxins A (SEA) and B (SEB) are classical models of superantigens (SAg), which induce potent T-cell-stimulating activity by forming complexes with MHC class II molecules on antigen-presenting cells. This large-scale activation of T-cells is accompanied by increased production of cytokines such as interferon-γ (IFN-γ). Additionally, as we previously reported, IFN-γ-producing CD8(+) T cells act as "helper cells," supporting the ability of dendritic cells to produce interleukin-12 (IL-12)p70. Here, we show that DC pulsed with SAg promote the enhancement of anti-tumor immunity. Murine bone marrow-derived dendritic cells (DC) were pulsed with OVA(257-264) (SIINFEKL), which is an H-2Kb target epitope of EG7 [ovalbumin (OVA)-expressing EL4] cell lines, in the presence of SEA and SEB and were subcutaneously injected into naïve C57BL/6 mice. SAg plus OVA(257-264)-pulsed DC vaccine strongly enhanced peptide-specific CD8(+) T cells exhibiting OVA(257-264)-specific cytotoxic activity and IFN-γ production, leading to the induction of protective immunity against EG7 tumors. Furthermore, cyclophosphamide (CY) added to SAg plus tumor-antigens (OVA(257-264), tumor lysate, or TRP-2) pulsed DC immunization markedly enhanced tumor-specific T-cell expansion and had a significant therapeutic effect against various tumors (EG7, 2LL, and B16). Superantigens are potential candidates for enhancing tumor immunity in DC vaccines.

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Testing mouse mammary tumor virus superantigen as adjuvant in cytotoxic T‐lymphocyte responses against a melanoma tumor antigen

Cited by 4 publications

References 37 publications

Potent antitumor effect elicited by superantigen‐linked tumor cells transduced with heat shock protein 70 gene

Potent antitumor effect elicited by superantigen‐linked tumor cells transduced with heat shock protein 70 gene

Nucleocapsid of rabies virus improve immune response of an inactivated avian influenza vaccine

Enhanced anti-tumor immunity by superantigen-pulsed dendritic cells

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