Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity

被引:32
作者
Ding, Ying [1 ]
Seow, See Voon [1 ]
Huang, Chiung Hui [1 ]
Liew, Lee Mei [1 ]
Lim, Yaw Chyn [2 ,3 ,4 ]
Kuo, I. Chun [1 ]
Chua, Kaw Yan [1 ,4 ]
机构
[1] Natl Univ Singapore, Dept Paediat, Yong Loo Lin Sch Med, Singapore 119260, Singapore
[2] Natl Univ Singapore, Dept Pathol, Yong Loo Lin Sch Med, Singapore 119260, Singapore
[3] Natl Univ Singapore, Dept Physiol, Yong Loo Lin Sch Med, Singapore 119260, Singapore
[4] Natl Univ Singapore, Immunol Programme, Ctr Life Sci, Singapore 119260, Singapore
基金
英国医学研究理事会;
关键词
adjuvant; dendritic cells; fungal immunomodulatory protein Fve; human papillomavirus-16 E7; immunotherapy; CD4(+) T-CELLS; VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS; DENDRITIC CELLS; CERVICAL-CANCER; IFN-GAMMA; FLAMMULINA-VELUTIPES; INTERFERON-GAMMA; ADOPTIVE IMMUNOTHERAPY; VACCINE DEVELOPMENT;
D O I
10.1111/j.1365-2567.2009.03099.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
P>Fve is a fungal protein isolated from the golden needle mushroom Flammulina velutipes and has previously been reported to trigger immunological responses in both mouse and human lymphocytes. In this study, we evaluated the potential application of Fve as an adjuvant for tumour immunotherapy and examined the underlying mechanism(s). When the human papillomavirus (HPV)-16 E7 oncoprotein was used as a model antigen, mice coimmunized with HPV-16 E7 and Fve showed enhanced production of HPV-16 E7-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells as compared with mice immunized with HPV-16 E7 alone. Tumour protection assays showed that 60% of mice coimmunized with HPV-16 E7 plus Fve, as compared with 20% of those immunized only with HPV-16 E7, remained tumour-free for up to 167 days after challenge with the tumour cells. Tumour therapeutic assays showed that HPV-16 E7 plus Fve treatment significantly prolonged the survival of tumour-bearing mice as compared with those treated only with HPV-16 E7. In vivo cell depletion and adoptive T-cell transfer assays showed that CD4(+) and CD8(+) T cells and IFN-gamma played critical roles in conferring the antitumour effects. Interestingly, Fve could stimulate the maturation of splenic dendritic cells in vivo and induce antigen-specific CD8(+) T-cell immune responses. In summary, Fve has potent adjuvant properties that enhance T helper type 1 antigen-specific humoral and cellular immune responses which confer strong antitumour effects. The use of Fve as an adjuvant could be an attractive alternative to the current vaccination strategy for cancer immunotherapy.
引用
收藏
页码:e881 / e894
页数:14
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