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MHC-Ig induces memory T cell formation in vivo and inhibits tumour growth.

Schütz C, Zoso A, Peng S, Bennett JD, Schneck JP, Oelke M - Immun Inflamm Dis (2014)

Bottom Line: Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells.Furthermore, B6 mice immunized with (pep-)MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model.Thus, soluble (pep-)MHC-Ig molecules represent a powerful tool for active immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Johns Hopkins Institute of Cell Engineering Baltimore, Maryland, 21205.

ABSTRACT
Induction of a T cell mediated immune response is critical for the eradication of viral infections and tumours. Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells. Furthermore, immobilized (pep-)MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use of (pep-)MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo. (SIY-)K(b)-Ig immunization, together with the pre-activation by an anti-CD40 monoclonal antibody, is able to stimulate a strong expansion of adoptively transferred 2C transgenic T cells and the formation of long term antigen-specific memory T cells. In addition, mechanistic studies show that the (pep-)MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized with (pep-)MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model. Thus, soluble (pep-)MHC-Ig molecules represent a powerful tool for active immunotherapy.

No MeSH data available.


Related in: MedlinePlus

Inhibition of B16-SIY tumour growth in SIY−Kb-Ig immunized mice. (A and B) On day −17 mice were injected intra peritoneal (i.p.) with anti-CD40 mAb. One day later mice were s.c. immunized with SIY−Kb-Ig (blue line), QL9−Ld-Ig (red line) or a combination of TRP2−Kb-Ig and gp100−Db-Ig (green line). On day −2 mice were boosted with additional pep−MHC-Ig and subsequently injected with B16-SIY tumour cells on day 0. The control group was treated with anti-CD40 mAb and PBS injections (black line). Tumour size was measured as surface area (mm2) at indicated days. The area under curve (AUC) is displayed in (C). (C) Significance was calculated over the entire experiment by AUC for each mice (P < 0.05 by ANOVA with Tukey's post-test) * indicates significant difference of each treatment group (blue, red and green bar) from control group (black bar).
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fig06: Inhibition of B16-SIY tumour growth in SIY−Kb-Ig immunized mice. (A and B) On day −17 mice were injected intra peritoneal (i.p.) with anti-CD40 mAb. One day later mice were s.c. immunized with SIY−Kb-Ig (blue line), QL9−Ld-Ig (red line) or a combination of TRP2−Kb-Ig and gp100−Db-Ig (green line). On day −2 mice were boosted with additional pep−MHC-Ig and subsequently injected with B16-SIY tumour cells on day 0. The control group was treated with anti-CD40 mAb and PBS injections (black line). Tumour size was measured as surface area (mm2) at indicated days. The area under curve (AUC) is displayed in (C). (C) Significance was calculated over the entire experiment by AUC for each mice (P < 0.05 by ANOVA with Tukey's post-test) * indicates significant difference of each treatment group (blue, red and green bar) from control group (black bar).

Mentions: The effects of pep−MHC-Ig immunization were also analyzed in a melanoma tumour prevention model. Wild type B6 mice were pretreated with anti-CD40 (day −17) and one day later (day −16) immunized with 250 µg/mouse SIY−Kb-Ig, QL9−Ld-Ig or a combination of TRP2−Kb-Ig and gp100−Db-Ig dimer. On day −2 animals received an additional booster immunization with 50 µg/mouse pep−MHC-Ig and B16-SIY tumour cells were administered on day 0 s.c. (Fig. 6A). Mice that were immunized with different pep−MHC-Ig showed a delayed tumour growth with a statistically significant difference already seen at day 7. By day 19 mice immunized with QL9−Ld-Ig had the smallest tumour burden, with an average tumour size of 92.76 mm2 (±88 mm2), followed by 99.82 mm2 (±82 mm2) for mice treated with SIY−Kb-Ig and 113.08 mm2 (±71 mm2) for TRP2−Kb-Ig and gp100−Db-Ig treated mice (Fig. 6B). Control animals showed the highest tumour burden of 217.51 mm2 (±32 mm2). Total tumour growth, seen as area under the curve (AUC), was significantly lower** (P < 0.05) for SIY−Kb-Ig (200.25 ± 161 mm2), QL9−Ld-Ig (249.58 ± 252 mm2) and TRP2−Kb/gp100−Db-Ig (229.42 ± 242 mm2) immunized mice than animals from the control group (657.76 ± 182 mm2) (Fig. 6C). Thus, SIY−Kb-Ig, QL9−Ld-Ig and TRP2−Kb/gp100−Db-Ig immunization induces a protective endogenous T cell response that has a significant anti-tumour activity in a B16-SIY melanoma model.


MHC-Ig induces memory T cell formation in vivo and inhibits tumour growth.

Schütz C, Zoso A, Peng S, Bennett JD, Schneck JP, Oelke M - Immun Inflamm Dis (2014)

Inhibition of B16-SIY tumour growth in SIY−Kb-Ig immunized mice. (A and B) On day −17 mice were injected intra peritoneal (i.p.) with anti-CD40 mAb. One day later mice were s.c. immunized with SIY−Kb-Ig (blue line), QL9−Ld-Ig (red line) or a combination of TRP2−Kb-Ig and gp100−Db-Ig (green line). On day −2 mice were boosted with additional pep−MHC-Ig and subsequently injected with B16-SIY tumour cells on day 0. The control group was treated with anti-CD40 mAb and PBS injections (black line). Tumour size was measured as surface area (mm2) at indicated days. The area under curve (AUC) is displayed in (C). (C) Significance was calculated over the entire experiment by AUC for each mice (P < 0.05 by ANOVA with Tukey's post-test) * indicates significant difference of each treatment group (blue, red and green bar) from control group (black bar).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig06: Inhibition of B16-SIY tumour growth in SIY−Kb-Ig immunized mice. (A and B) On day −17 mice were injected intra peritoneal (i.p.) with anti-CD40 mAb. One day later mice were s.c. immunized with SIY−Kb-Ig (blue line), QL9−Ld-Ig (red line) or a combination of TRP2−Kb-Ig and gp100−Db-Ig (green line). On day −2 mice were boosted with additional pep−MHC-Ig and subsequently injected with B16-SIY tumour cells on day 0. The control group was treated with anti-CD40 mAb and PBS injections (black line). Tumour size was measured as surface area (mm2) at indicated days. The area under curve (AUC) is displayed in (C). (C) Significance was calculated over the entire experiment by AUC for each mice (P < 0.05 by ANOVA with Tukey's post-test) * indicates significant difference of each treatment group (blue, red and green bar) from control group (black bar).
Mentions: The effects of pep−MHC-Ig immunization were also analyzed in a melanoma tumour prevention model. Wild type B6 mice were pretreated with anti-CD40 (day −17) and one day later (day −16) immunized with 250 µg/mouse SIY−Kb-Ig, QL9−Ld-Ig or a combination of TRP2−Kb-Ig and gp100−Db-Ig dimer. On day −2 animals received an additional booster immunization with 50 µg/mouse pep−MHC-Ig and B16-SIY tumour cells were administered on day 0 s.c. (Fig. 6A). Mice that were immunized with different pep−MHC-Ig showed a delayed tumour growth with a statistically significant difference already seen at day 7. By day 19 mice immunized with QL9−Ld-Ig had the smallest tumour burden, with an average tumour size of 92.76 mm2 (±88 mm2), followed by 99.82 mm2 (±82 mm2) for mice treated with SIY−Kb-Ig and 113.08 mm2 (±71 mm2) for TRP2−Kb-Ig and gp100−Db-Ig treated mice (Fig. 6B). Control animals showed the highest tumour burden of 217.51 mm2 (±32 mm2). Total tumour growth, seen as area under the curve (AUC), was significantly lower** (P < 0.05) for SIY−Kb-Ig (200.25 ± 161 mm2), QL9−Ld-Ig (249.58 ± 252 mm2) and TRP2−Kb/gp100−Db-Ig (229.42 ± 242 mm2) immunized mice than animals from the control group (657.76 ± 182 mm2) (Fig. 6C). Thus, SIY−Kb-Ig, QL9−Ld-Ig and TRP2−Kb/gp100−Db-Ig immunization induces a protective endogenous T cell response that has a significant anti-tumour activity in a B16-SIY melanoma model.

Bottom Line: Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells.Furthermore, B6 mice immunized with (pep-)MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model.Thus, soluble (pep-)MHC-Ig molecules represent a powerful tool for active immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Johns Hopkins Institute of Cell Engineering Baltimore, Maryland, 21205.

ABSTRACT
Induction of a T cell mediated immune response is critical for the eradication of viral infections and tumours. Soluble peptide-loaded major histocompatibility complex-Ig ((pep-)MHC-Ig) have been shown to bind their cognate ligands, T cell receptor, with high affinity, and are successfully used to visualize antigen-specific T cells. Furthermore, immobilized (pep-)MHC-Ig can activate and expand antigen-specific T cells in vitro and in vivo. In this study, we investigate the use of (pep-)MHC-Ig as a potential strategy to modulate antigen specific T cell immune responses in vivo. (SIY-)K(b)-Ig immunization, together with the pre-activation by an anti-CD40 monoclonal antibody, is able to stimulate a strong expansion of adoptively transferred 2C transgenic T cells and the formation of long term antigen-specific memory T cells. In addition, mechanistic studies show that the (pep-)MHC-Ig molecules directly activate T cells in vivo without requiring uptake and reprocessing by antigen-presenting cells. Furthermore, B6 mice immunized with (pep-)MHC-Ig molecules inhibit tumour growth in a B16-SIY melanoma prevention model. Thus, soluble (pep-)MHC-Ig molecules represent a powerful tool for active immunotherapy.

No MeSH data available.


Related in: MedlinePlus