PURPOSE: Tumor-derived exosomes (TEX) have been proposed as a new kind of cancer vaccine; however, their in vivo antitumor effects are not satisfactory. In order to further improve the efficacy of vaccination with TEX, we investigated whether interleukin-2 (IL-2) genetic modification of tumor cells can make IL-2 presence in the exosomes, thus increasing antitumor effects of the TEX. METHODS: E.G7-OVA tumor cells expressing Ovalbumin (OVA) as a tumor model antigen were used to prepare TEX by serial centrifugation and sucrose gradients ultracentrifugation. To demonstrate their antitumor effects, IL-2-containing exosomes (Exo/IL-2) were injected subcutaneously into C57BL/C mice: either bearing tumor or followed by tumor inoculation. RESULTS: We found IL-2 within those exosomes as detected by both ELISA and Western blot. Vaccination with these Exo/IL-2 could induce antigen-specific Th1-polarized immune response and Cytotoxic T lymphocytes (CTL) more efficiently, resulting in more significant inhibition of tumor growth. CD8(+) T cells are the main effector cells, however, CD4(+) T cells, and NK cells are also involved in the induction of antitumor response of this approach. CONCLUSIONS: Our results demonstrate that IL-2 genetic modification of tumor cells can make the TEX contain IL-2 with the increased antitumor effects, representing a promising way of exosome-based tumor vaccine.
PURPOSE: Tumor-derived exosomes (TEX) have been proposed as a new kind of cancer vaccine; however, their in vivo antitumor effects are not satisfactory. In order to further improve the efficacy of vaccination with TEX, we investigated whether interleukin-2 (IL-2) genetic modification of tumor cells can make IL-2 presence in the exosomes, thus increasing antitumor effects of the TEX. METHODS: E.G7-OVA tumor cells expressing Ovalbumin (OVA) as a tumor model antigen were used to prepare TEX by serial centrifugation and sucrose gradients ultracentrifugation. To demonstrate their antitumor effects, IL-2-containing exosomes (Exo/IL-2) were injected subcutaneously into C57BL/C mice: either bearing tumor or followed by tumor inoculation. RESULTS: We found IL-2 within those exosomes as detected by both ELISA and Western blot. Vaccination with these Exo/IL-2 could induce antigen-specific Th1-polarized immune response and Cytotoxic T lymphocytes (CTL) more efficiently, resulting in more significant inhibition of tumor growth. CD8(+) T cells are the main effector cells, however, CD4(+) T cells, and NK cells are also involved in the induction of antitumor response of this approach. CONCLUSIONS: Our results demonstrate that IL-2 genetic modification of tumor cells can make the TEX contain IL-2 with the increased antitumor effects, representing a promising way of exosome-based tumor vaccine.
Authors: Pinar Kanlikilicer; Mohammed H Rashed; Recep Bayraktar; Rahul Mitra; Cristina Ivan; Burcu Aslan; Xinna Zhang; Justyna Filant; Andreia M Silva; Cristian Rodriguez-Aguayo; Emine Bayraktar; Martin Pichler; Bulent Ozpolat; George A Calin; Anil K Sood; Gabriel Lopez-Berestein Journal: Cancer Res Date: 2016-10-14 Impact factor: 12.701
Authors: Eva U Wieckowski; Carmen Visus; Marta Szajnik; Miroslaw J Szczepanski; Walter J Storkus; Theresa L Whiteside Journal: J Immunol Date: 2009-08-19 Impact factor: 5.422