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Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction.

Ménager J, Gorin JB, Maurel C, Drujont L, Gouard S, Louvet C, Chérel M, Faivre-Chauvet A, Morgenstern A, Bruchertseifer F, Davodeau F, Gaschet J, Guilloux Y - PLoS ONE (2015)

Bottom Line: Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells).We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment.These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established.

View Article: PubMed Central - PubMed

Affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.

ABSTRACT
Ionizing radiation induces direct and indirect killing of cancer cells and for long has been considered as immunosuppressive. However, this concept has evolved over the past few years with the demonstration that irradiation can increase tumor immunogenicity and can actually favor the implementation of an immune response against tumor cells. Adoptive T-cell transfer (ACT) is also used to treat cancer and several studies have shown that the efficacy of this immunotherapy was enhanced when combined with radiation therapy. α-Radioimmunotherapy (α-RIT) is a type of internal radiotherapy which is currently under development to treat disseminated tumors. α-particles are indeed highly efficient to destroy small cluster of cancer cells with minimal impact on surrounding healthy tissues. We thus hypothesized that, in the setting of α-RIT, an immunotherapy like ACT, could benefit from the immune context induced by irradiation. Hence, we decided to further investigate the possibilities to promote an efficient and long-lasting anti-tumor response by combining α-RIT and ACT. To perform such study we set up a multiple myeloma murine model which express the tumor antigen CD138 and ovalbumine (OVA). Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells). We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment. These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established.

No MeSH data available.


Related in: MedlinePlus

In vivo tumor growth of 5T33-OVA.Growth comparison of established tumors 5T33 versus 5T33-OVA. Animals were injected subcutaneously with 2x106 tumor cells (n = 5 mice per group).
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pone.0130249.g003: In vivo tumor growth of 5T33-OVA.Growth comparison of established tumors 5T33 versus 5T33-OVA. Animals were injected subcutaneously with 2x106 tumor cells (n = 5 mice per group).

Mentions: To complete the validation of our model, we investigated the in vivo growth capability of 5T33-OVA after subcutaneous injection. Such study was performed by injection of 2x106 of 5T33 or 5T33-OVA in the right flank of C57BL6/KalwRij mice and tumor progression was monitored. As shown in Fig 3, no growth difference was detected between parental 5T33 and 5T33–OVA (2 way ANOVA, p<0,05). These data show that there is a minimum impact of OVA expression on tumor cell development in vivo.


Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction.

Ménager J, Gorin JB, Maurel C, Drujont L, Gouard S, Louvet C, Chérel M, Faivre-Chauvet A, Morgenstern A, Bruchertseifer F, Davodeau F, Gaschet J, Guilloux Y - PLoS ONE (2015)

In vivo tumor growth of 5T33-OVA.Growth comparison of established tumors 5T33 versus 5T33-OVA. Animals were injected subcutaneously with 2x106 tumor cells (n = 5 mice per group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476754&req=5

pone.0130249.g003: In vivo tumor growth of 5T33-OVA.Growth comparison of established tumors 5T33 versus 5T33-OVA. Animals were injected subcutaneously with 2x106 tumor cells (n = 5 mice per group).
Mentions: To complete the validation of our model, we investigated the in vivo growth capability of 5T33-OVA after subcutaneous injection. Such study was performed by injection of 2x106 of 5T33 or 5T33-OVA in the right flank of C57BL6/KalwRij mice and tumor progression was monitored. As shown in Fig 3, no growth difference was detected between parental 5T33 and 5T33–OVA (2 way ANOVA, p<0,05). These data show that there is a minimum impact of OVA expression on tumor cell development in vivo.

Bottom Line: Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells).We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment.These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established.

View Article: PubMed Central - PubMed

Affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.

ABSTRACT
Ionizing radiation induces direct and indirect killing of cancer cells and for long has been considered as immunosuppressive. However, this concept has evolved over the past few years with the demonstration that irradiation can increase tumor immunogenicity and can actually favor the implementation of an immune response against tumor cells. Adoptive T-cell transfer (ACT) is also used to treat cancer and several studies have shown that the efficacy of this immunotherapy was enhanced when combined with radiation therapy. α-Radioimmunotherapy (α-RIT) is a type of internal radiotherapy which is currently under development to treat disseminated tumors. α-particles are indeed highly efficient to destroy small cluster of cancer cells with minimal impact on surrounding healthy tissues. We thus hypothesized that, in the setting of α-RIT, an immunotherapy like ACT, could benefit from the immune context induced by irradiation. Hence, we decided to further investigate the possibilities to promote an efficient and long-lasting anti-tumor response by combining α-RIT and ACT. To perform such study we set up a multiple myeloma murine model which express the tumor antigen CD138 and ovalbumine (OVA). Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells). We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment. These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established.

No MeSH data available.


Related in: MedlinePlus