Scientific Publications by FDA Staff
J Transl Med 2010 Nov 10;8:116
Interleukin-13 receptor ¿2 DNA prime boost vaccine induces tumor immunity in murine tumor models.
Nakashima H, Fujisawa T, Husain SR, Puri RK
BACKGROUND: DNA vaccines represent an attractive approach for cancer treatment by inducing active T cell and B cell immune responses to tumor antigens. Previous studies have shown that interleukin-13 receptor ¿2 chain (IL-13R¿2), a tumor-associated antigen is a promising target for cancer immunotherapy as high levels of IL-13R¿2 are expressed on a variety of human tumors. To enhance the effectiveness of DNA vaccine, we used extracellular domain of IL-13R¿2 (ECD¿2) as a protein-boost against murine tumor models. METHODS: We have developed murine models of tumors naturally expressing IL-13R¿2 (MCA304 sarcoma, 4T1 breast carcinoma) and D5 melanoma tumors transfected with human IL-13R¿2 in syngeneic mice and examined the antitumor activity of DNA vaccine expressing IL-13R¿2 gene with or without ECD¿2 protein mixed with CpG and IFA adjuvants as a boost vaccine. RESULTS: Mice receiving IL-13R¿2 DNA vaccine boosted with ECD¿2 protein were superior in exhibiting inhibition of tumor growth, compared to mice receiving DNA vaccine alone, in both prophylactic and therapeutic vaccine settings. In addition, prime-boost vaccination significantly prolonged the survival of mice compared to DNA vaccine alone. Furthermore, ECD¿2 booster vaccination increased IFN-¿ production and CTL activity against tumor expressing IL-13R¿2. The immunohistochemical analysis showed the infiltration of CD4 and CD8 positive T cells and IFN-¿-induced chemokines (CXCL9 and CXCL10) in regressing tumors of immunized mice. Finally, the prime boost strategy was able to reduce immunosuppressive CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in the spleen and tumor of vaccinated mice. CONCLUSION: These results suggest that immunization with IL-13R¿2 DNA vaccine followed by ECD¿2 boost mixed with CpG and IFA adjuvants inhibits tumor growth in T cell dependent manner. Thus our results show an enhancement of efficacy of IL-13R¿2 DNA vaccine with ECD¿2 protein boost and offers an exciting approach in the development of new DNA vaccine targeting IL-13R¿2 for cancer immunotherapy.
|Category: Journal Article|
|PubMed ID: #21067607||DOI: 10.1186/1479-5876-8-116|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|