Fu-Sheng Gao1, Yu-Tao Zhan2, Xu-Dong Wang1, Chuan Zhang1. 1. a Department of Medicine , Beijing Tongren Hospital, Capital Medical University , Beijing , China. 2. b Department of Gastroenterology , Beijing Tongren Hospital, Capital Medical University , Beijing , China.
Abstract
AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy; however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L) has been exploited for its ability to increase the proliferation of dendritic cells (DCs). The aim of the present study was to investigate whether co-administration of an adjuvant plasmid expressing mouse Flt3L and a DNA vaccine of the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice intramuscularly (i.m.), followed by electroporation. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model of MUC1-expressing tumors was established. RESULTS: The results showed that co-administration of an adjuvant plasmid and a DNA vaccine stimulated the production of higher titers of specific antibodies and a T cell response and suppressed the growth of subcutaneous tumors expressing MUC1. Collectively, our results indicate that a plasmid expressing murine Flt3L could stimulate stronger immune responses. CONCLUSION: These observations emphasize the potential of Flt3L as an adjuvant for colon cancer DNA vaccines.
AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy; however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L) has been exploited for its ability to increase the proliferation of dendritic cells (DCs). The aim of the present study was to investigate whether co-administration of an adjuvant plasmid expressing mouseFlt3L and a DNA vaccine of the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice intramuscularly (i.m.), followed by electroporation. The humoral and cellular immune responses after immunization were examined by enzyme linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To evaluate the anti-tumor efficacy of the plasmids, a mouse model of MUC1-expressing tumors was established. RESULTS: The results showed that co-administration of an adjuvant plasmid and a DNA vaccine stimulated the production of higher titers of specific antibodies and a T cell response and suppressed the growth of subcutaneous tumors expressing MUC1. Collectively, our results indicate that a plasmid expressing murineFlt3L could stimulate stronger immune responses. CONCLUSION: These observations emphasize the potential of Flt3L as an adjuvant for colon cancer DNA vaccines.
Entities:
Keywords:
DNA vaccine; Fms-like tyrosine kinase 3-ligand; MUC1; colon cancer
Authors: Amy Haseley Thorne; Kirsten N Malo; Ashley J Wong; Tricia T Nguyen; Neil Cooch; Charles Reed; Jian Yan; Kate E Broderick; Trevor R F Smith; Emma L Masteller; Laurent Humeau Journal: Front Immunol Date: 2020-02-25 Impact factor: 7.561