Haemin Park1,2, Matthew Gladstone3, Crystal Shanley2, Raymond Goodrich2, Amanda Guth1. 1. Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA. 2. Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. 3. California Institute of Technology, Pasadena, CA, USA.
Abstract
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 IFNγ 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.
BACKGROUND: With the recent interest in personalized medicine for cancerpatients 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 IFNγ production and generation of tumour cell-specific IgG. Moreover, when formulated with an adjuvant ('Innocell vaccine') and tested in different murinetumour 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 cancerpatients.
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