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Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice

Identifieur interne : 000082 ( Istex/Corpus ); précédent : 000081; suivant : 000083

Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice

Auteurs : Catherine J. Lees ; Vasso Apostolopoulos ; Bruce Acres ; Ian Ramshaw ; Alistair Ramsay ; Chin.-Swee Ong ; Ian F. C Mckenzie

Source :

RBID : ISTEX:0436D241201D03E24ACFA04DF57DB24A63713B39

English descriptors

Abstract

Abstract: Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC restricted CD8+ cytotoxic T cells. We now demonstrate that in MUC1/HLA-A2 transgenic mice, IL-12 gives enhanced CTL, CTLp and tumor protection. CTLp in MUC1 transgenic mice with M-FP were 1/55,000, and with IL-12, this increased to 1/19,000, with improved tumor protection. Thus, IL-12 is important for effective CTL responses to MUC1 in transgenic mice.

Url:
DOI: 10.1016/S0264-410X(00)00065-7

Links to Exploration step

ISTEX:0436D241201D03E24ACFA04DF57DB24A63713B39

Le document en format XML

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<note type="content">Fig. 1: Average CTLp frequencies from (A) BALB/c mice immunized I.P (×1 or ×3) with either 5 μg M-FP (□) or 5 μg M-FP+murine rIL-12 (■) (1 μg/mouse/day IP×5 days) (3 mice/group). The CTLp frequencies from mice injected with rIL-12 only were <1/106 (not shown); (B) MUC1 transgenic mice immunized I.P (either ×1 or ×3) with either 5 μg M-FP (□) or 5 μg M-FP+VVIL-12 (1×107 pfu/ml) (▨). The CTLp frequency for mice injected both ×1 and ×3 with VVIL-12 alone were <1/106 (not shown); and (C) A2-MUC1 transgenic mice immunized I.P (×3) with either 5 μg M-FP □ or 5 μg M-FP+VVIL-12 (1×107 pfu/ml) ▨. HLA-A2 restricted, MUC1 positive CTL precursors were determined using the MCF-7 target cell line and MUC1, H-2d CTL precursors were determined using the MUC1+ P815 target cell line. The CTLp frequencies from mice injected with VVIL-12 alone were <1/106 on both target cell lines (not shown).</note>
<note type="content">Fig. 2: MUC1 transgenic tumor challenge. (A) MUC1 transgenic mice (5–6/group) were injected with either pH 9.0 buffer (•), 5 μg M-FP (■), or 5 μg M-FP+VVIL-12 (▴) (1×107 pfu/ml) on days 0, 7 and 14 and challenged with 3.5×106 P815-MUC1 tumor cells on day 22 and tumor growth measured. (B) MUC1 transgenic mice (7–9/group) immunized intraperitoneally on days 0, 7 and 14 with either 5 μg M-FP, 5 μg M-FP+VV (1×107 pfu/ml), 5 μg M-FP+VVIL-12 (1×107 pfu/ml) or VVIL-12 (1×107 pfu/ml) and challenged on day 21 with 1×107 P815-MUC1 tumor cells. The number of mice with palpable tumors 30 days later are represented as a percentage of the total number of mice in each group with a tumor (± SE). Fisher’s Exact Test was used to determine the statistical significance of the data.</note>
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<ce:simple-para>Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC restricted CD8
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cytotoxic T cells. We now demonstrate that in MUC1/HLA-A2 transgenic mice, IL-12 gives enhanced CTL, CTLp and tumor protection. CTLp in MUC1 transgenic mice with M-FP were 1/55,000, and with IL-12, this increased to 1/19,000, with improved tumor protection. Thus, IL-12 is important for effective CTL responses to MUC1 in transgenic mice.</ce:simple-para>
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<abstract lang="en">Abstract: Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC restricted CD8+ cytotoxic T cells. We now demonstrate that in MUC1/HLA-A2 transgenic mice, IL-12 gives enhanced CTL, CTLp and tumor protection. CTLp in MUC1 transgenic mice with M-FP were 1/55,000, and with IL-12, this increased to 1/19,000, with improved tumor protection. Thus, IL-12 is important for effective CTL responses to MUC1 in transgenic mice.</abstract>
<note type="content">Section title: Short Communication</note>
<note type="content">Fig. 1: Average CTLp frequencies from (A) BALB/c mice immunized I.P (×1 or ×3) with either 5 μg M-FP (□) or 5 μg M-FP+murine rIL-12 (■) (1 μg/mouse/day IP×5 days) (3 mice/group). The CTLp frequencies from mice injected with rIL-12 only were <1/106 (not shown); (B) MUC1 transgenic mice immunized I.P (either ×1 or ×3) with either 5 μg M-FP (□) or 5 μg M-FP+VVIL-12 (1×107 pfu/ml) (▨). The CTLp frequency for mice injected both ×1 and ×3 with VVIL-12 alone were <1/106 (not shown); and (C) A2-MUC1 transgenic mice immunized I.P (×3) with either 5 μg M-FP □ or 5 μg M-FP+VVIL-12 (1×107 pfu/ml) ▨. HLA-A2 restricted, MUC1 positive CTL precursors were determined using the MCF-7 target cell line and MUC1, H-2d CTL precursors were determined using the MUC1+ P815 target cell line. The CTLp frequencies from mice injected with VVIL-12 alone were <1/106 on both target cell lines (not shown).</note>
<note type="content">Fig. 2: MUC1 transgenic tumor challenge. (A) MUC1 transgenic mice (5–6/group) were injected with either pH 9.0 buffer (•), 5 μg M-FP (■), or 5 μg M-FP+VVIL-12 (▴) (1×107 pfu/ml) on days 0, 7 and 14 and challenged with 3.5×106 P815-MUC1 tumor cells on day 22 and tumor growth measured. (B) MUC1 transgenic mice (7–9/group) immunized intraperitoneally on days 0, 7 and 14 with either 5 μg M-FP, 5 μg M-FP+VV (1×107 pfu/ml), 5 μg M-FP+VVIL-12 (1×107 pfu/ml) or VVIL-12 (1×107 pfu/ml) and challenged on day 21 with 1×107 P815-MUC1 tumor cells. The number of mice with palpable tumors 30 days later are represented as a percentage of the total number of mice in each group with a tumor (± SE). Fisher’s Exact Test was used to determine the statistical significance of the data.</note>
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