title: Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction.
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.
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Ménager
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Gorin
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maurel
authors.affiliation: INSERM UMR 1064 -ITUN, Nantes, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Drujont
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gouard
authors.affiliation: INSERM UMR 1064 -ITUN, Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Louvet
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France; Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Chérel
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France; CHU Nantes, Nuclear Medicine Department, Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Morgenstern
authors.affiliation: European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bruchertseifer
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Davodeau
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Gaschet
authors.affiliation: CRCNA-UMR 892 INSERM, Nantes, France; 6299 CNRS, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Guilloux
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001729:Bismuth / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D016499:Radioimmunotherapy / Q000379:methods; D053668:Syndecan-1 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D053668:Syndecan-1; D010047:Ovalbumin; D001729:Bismuth