A novel cancer immunotherapy utilizing autologous tumour tissue

被引:4
|
作者
Park, Haemin [1 ,2 ]
Gladstone, Matthew [3 ]
Shanley, Crystal [2 ]
Goodrich, Raymond [2 ]
Guth, Amanda [1 ]
机构
[1] Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USA
[2] Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA
[3] CALTECH, Pasadena, CA 91125 USA
关键词
cancer; cellular therapy; blood processing; cell culture; VACCINE; INACTIVATION; RIBOFLAVIN; CELLS;
D O I
10.1111/vox.12935
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumour vaccine trials have not produced convincing results due, in part to poor patient selection and inactivation methos that are harsh on the cells. These methods can alter protein structure and antigenic profiles making vaccine candidates ineffective in stimulating immune response to autochthonous tumour cells. Materials and methods We investigated a novel method for inactivating tumour cells that uses UVA/UVB light and riboflavin (vitamin B2) (RF + UV). RF + UV inactivates the tumour cells' ability to replicate, yet preserves tumour cell integrity and antigenicity. Results Our results demonstrate that proteins are preserved on the surface of RF + UV-inactivated tumour cells and that they are immunogenic via induction of dendritic cell maturation, increase in IFN gamma production and generation of tumour cell-specific IgG. Moreover, when formulated with an adjuvant ('Innocell vaccine') and tested in different murine tumour primary and metastatic disease models, decreased tumour growth, decreased metastatic disease and prolonged survival were observed. In addition, immune cells obtained from tumour tissue following vaccination had decreased exhausted and regulatory T cells, suggesting that activation of intra-tumoural T cells may be playing a role leading to reduced tumour growth. Conclusions These data suggest that the RF + UV inactivation of tumour cells may provide an efficacious method for generating autologous whole tumour cell vaccines for use in cancer patients.
引用
收藏
页码:525 / 535
页数:11
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