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Fas ligand DNA enhances a vaccination effect by coadministered DNA encoding a tumor antigen through augmenting production of antibody against the tumor antigen.

Zhong B, Ma G, Sato A, Shimozato O, Liu H, Li Q, Shingyoji M, Tada Y, Tatsumi K, Shimada H, Hiroshima K, Tagawa M - J Immunol Res (2015)

Bottom Line: Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood.We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone.These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China ; Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

ABSTRACT
Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, β-galactosidase (β-gal). Growth of β-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with β-gal and FasL DNA compared with those vaccinated with β-gal or FasL DNA. We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone. Subtype analysis of anti-β-gal antibody produced by the combination of β-gal and FasL DNA or β-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with β-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than β-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

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Antitumor effects produced by DNA immunization. BALB/c mice (n = 6 or 7) were treated with cardiotoxin and 5 days later with DNA (50 μg for each), pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL (FasL), pcDNA3/β-gal (β-gal) + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (β-gal + FasL). The mice were then inoculated with Colon 26/β-gal cells (1 × 106) 21 days after DNA injections. The tumor growth of mice injected with cDNA3/β-gal + pCAGGS/FasL was significantly retarded 21 days after the tumor inoculation compared with that of mice inoculated with pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, or pcDNA3/β-gal + pCAGGS. #P < 0.05.
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fig2: Antitumor effects produced by DNA immunization. BALB/c mice (n = 6 or 7) were treated with cardiotoxin and 5 days later with DNA (50 μg for each), pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL (FasL), pcDNA3/β-gal (β-gal) + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (β-gal + FasL). The mice were then inoculated with Colon 26/β-gal cells (1 × 106) 21 days after DNA injections. The tumor growth of mice injected with cDNA3/β-gal + pCAGGS/FasL was significantly retarded 21 days after the tumor inoculation compared with that of mice inoculated with pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, or pcDNA3/β-gal + pCAGGS. #P < 0.05.

Mentions: We investigated whether immunization with DNA encoding a putative tumor antigen achieved antitumor effects. We firstly transduced murine Colon 26 cells with the β-gal gene and confirmed that the growth of Colon 26/β-gal cells in vitro and in vivo was not different from parental Colon 26 cells. Syngeneic BALB/c mice were injected with cardiotoxin and then with DNA expressing the β-gal and/or FasL gene or vector DNA as a control. The mice were then inoculated with Colon 26/β-gal cells and the tumor volumes were monitored. Growth of Colon 26/β-gal cells was not statistically different among mice that were inoculated with vector DNA, pcDNA3/β-gal, or pCAGGS/FasL DNA (Figure 2), and the tumor growth in these mice was not different from that in naive mice (data not shown). In contrast, the tumor growth in mice that received both pcDNA3/β-gal and pCAGGS/FasL DNA was retarded compared with that in mice immunized with vector DNA, pcDNA3/β-gal, or pCAGGS/FasL DNA (P < 0.05). These data indicated that immunization of DNA encoding the β-gal or the FasL gene alone did not produce antitumor effects but a combinatory use of both DNA achieved vaccination effects.


Fas ligand DNA enhances a vaccination effect by coadministered DNA encoding a tumor antigen through augmenting production of antibody against the tumor antigen.

Zhong B, Ma G, Sato A, Shimozato O, Liu H, Li Q, Shingyoji M, Tada Y, Tatsumi K, Shimada H, Hiroshima K, Tagawa M - J Immunol Res (2015)

Antitumor effects produced by DNA immunization. BALB/c mice (n = 6 or 7) were treated with cardiotoxin and 5 days later with DNA (50 μg for each), pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL (FasL), pcDNA3/β-gal (β-gal) + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (β-gal + FasL). The mice were then inoculated with Colon 26/β-gal cells (1 × 106) 21 days after DNA injections. The tumor growth of mice injected with cDNA3/β-gal + pCAGGS/FasL was significantly retarded 21 days after the tumor inoculation compared with that of mice inoculated with pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, or pcDNA3/β-gal + pCAGGS. #P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352480&req=5

fig2: Antitumor effects produced by DNA immunization. BALB/c mice (n = 6 or 7) were treated with cardiotoxin and 5 days later with DNA (50 μg for each), pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL (FasL), pcDNA3/β-gal (β-gal) + pCAGGS, or pcDNA3/β-gal + pCAGGS/FasL (β-gal + FasL). The mice were then inoculated with Colon 26/β-gal cells (1 × 106) 21 days after DNA injections. The tumor growth of mice injected with cDNA3/β-gal + pCAGGS/FasL was significantly retarded 21 days after the tumor inoculation compared with that of mice inoculated with pcDNA3 + pCAGGS, pcDNA3 + pCAGGS/FasL, or pcDNA3/β-gal + pCAGGS. #P < 0.05.
Mentions: We investigated whether immunization with DNA encoding a putative tumor antigen achieved antitumor effects. We firstly transduced murine Colon 26 cells with the β-gal gene and confirmed that the growth of Colon 26/β-gal cells in vitro and in vivo was not different from parental Colon 26 cells. Syngeneic BALB/c mice were injected with cardiotoxin and then with DNA expressing the β-gal and/or FasL gene or vector DNA as a control. The mice were then inoculated with Colon 26/β-gal cells and the tumor volumes were monitored. Growth of Colon 26/β-gal cells was not statistically different among mice that were inoculated with vector DNA, pcDNA3/β-gal, or pCAGGS/FasL DNA (Figure 2), and the tumor growth in these mice was not different from that in naive mice (data not shown). In contrast, the tumor growth in mice that received both pcDNA3/β-gal and pCAGGS/FasL DNA was retarded compared with that in mice immunized with vector DNA, pcDNA3/β-gal, or pCAGGS/FasL DNA (P < 0.05). These data indicated that immunization of DNA encoding the β-gal or the FasL gene alone did not produce antitumor effects but a combinatory use of both DNA achieved vaccination effects.

Bottom Line: Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood.We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone.These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China ; Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.

ABSTRACT
Interaction of Fas and Fas ligand (FasL) plays an important role in the regulation of immune responses by inducing apoptosis of activated cells; however, a possible role of FasL in DNA vaccination has not been well understood. We examined whether administration of DNA encoding FasL gene enhanced antitumor effects in mice that were vaccinated with DNA expressing a putative tumor antigen gene, β-galactosidase (β-gal). Growth of β-gal-positive Colon 26 tumors was retarded in the syngeneic mice immunized with β-gal and FasL DNA compared with those vaccinated with β-gal or FasL DNA. We did not detect increased numbers of β-gal-specific CD8(+) T cells in lymph node of mice that received combination of β-gal and FasL DNA, but amounts of anti-β-gal antibody increased with the combination but not with β-gal or FasL DNA injection alone. Subtype analysis of anti-β-gal antibody produced by the combination of β-gal and FasL DNA or β-gal DNA injection showed that IgG2a amounts were greater in mice injected with both DNA than those with β-gal DNA alone, but IgG2b amounts were lower in both DNA-injected than β-gal DNA-injected mice. These data suggest that FasL is involved in boosting humoral immunity against a gene product encoded by coinjected DNA and enhances the vaccination effects.

Show MeSH
Related in: MedlinePlus