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  • In our study ES SCLC patients

    2019-04-22

    In our study, ES-SCLC patients in the CIT group were on average older than those in the control group. However, the multivariate analysis showed that age had no effect on the prognosis of these patients. Therefore, age was no a confounding factor, although it has been reported that effector cell function decreases in older people, and might be associated with reduced antitumor immunity in these patients [41].
    Conclusions
    Authors\' contributions
    Competing interests
    Acknowledgments This work was supported by the Jilin Provincial Science and Technology Department (Grants 20111807 and 20140414014 GH, and 20150101176 to JW.C.), the Platform Construction Project of Development and Reform Commission of Jilin Province (Grant 2014N147 to JW.C.), the Bethune Program B of Jilin University (Grant 2012202 to JW.C.), Key Clinical Project of the Ministry of Health of the People\'s Republic of China (Grant 2001133 to W.L), and National Major Scientific and Technological Special Project (Grant 2013ZX09102032 to JT.C).
    Introduction For over 60 years, aluminum salts (alum) were the only adjuvants approved for practical vaccination by the Food and Drug Administration [1] and have been extensively used in the prophylactic vaccination. Many researchers described that alum is a very effective adjuvant for promoting humoral immunity and Th2 type T-cell responses, but it is not an effective adjuvant for inducing Th1 immune responses [2,3]. The reasons behind the poor effectiveness of alum in promoting Th1 responses are not fully understood but may include the promotion of IL-4 secreting granulocytes [3] and the inhibition of IL-12 production by dendritic cysteine protease inhibitor [4]. Other studies have shown that alum combined with IL-12 can facilitate the induction of Th1 immune response [5,6]. Despite the realized efforts, it is surprising that yet is no consensus regarding the mechanisms by which alum potentiate the immune system. Whilst prophylactic vaccination aims to the induction of antibody response, the therapeutic vaccination needs the generation of a potent cell-mediated immune response. In this study we want to investigate if aluminum hydroxide [Al(OH)3] adjuvant could promote a cell-mediated immune response when is combined with an antigen. To prove this concept we selected a human papillomavirus (HPV) type 16 associated tumor model in mice, particularly the TC-1 model, because these tumor cells strongly express MHC class I and constitutes a suitable model to evaluate therapies that require the generation of cell-mediated immunity, particularly T cell-mediated immunity [7]. The selected antigen for this study was the LALF32-51-E7. The LALF32-51-E7 is a fusion protein comprising a cell penetrating peptide and HPV-16 E7 mutein that was designed to be an antigen of a protein-based therapeutic vaccine against HPV-16 induced lesions [8]. In this study we demonstrated that LALF32-51-E7 combined with aluminum hydroxide adjuvant promotes a Th1 immune response and consequently an anti-tumor response in the TC-1 tumor model.
    Materials and methods
    Results
    Discussion Taking into account the findings mentioned previously, we investigated if the therapeutic vaccination with our antigen LALF32-51-E7 combined with Al(OH)3 adjuvant could generate a cell-mediated immune response. In a previous study in the TC-1 model we demonstrated that the immunization with LALF32-51-E7 fusion protein without adjuvant induces a potent anti-tumor response and their combination with VSSP adjuvant promotes a benefit in the survival of the immunized animals [8]. In this study, we used VSSP as our model of Th1 polarizing adjuvant and we developed TC-1* cells more tumourigenic as compared to the original cell line to test the capacity of Al(OH)3 as adjuvant. We have found that the use of Al(OH)3 in combination with our vaccine antigen induced a predominantly Th1 immune response as well as VSSP.