title: Radioimmunotherapy for Treatment of Acute Leukemia.
abstract: Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL.
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bodet-Milin
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, Nantes University Hospital, France; Department of Nuclear Medicine, ICO-René Gauducheau, Saint-Herblain, France. Electronic address: francoise.bodere@chu-nantes.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodéré
authors.affiliation: Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eugène
authors.affiliation: CRCNA, INSERM U892, Nantes University, France.
authors.forename: François
authors.initials: F
authors.lastname: Guérard
authors.affiliation: CRCNA, INSERM U892, Nantes University, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Gaschet
authors.affiliation: Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Bailly
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Mougin
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Bourgeois
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, Nantes University Hospital, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Department of Nuclear Medicine, ICO-René Gauducheau, Saint-Herblain, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Chérel
authors.affiliation: CRCNA, INSERM U892, Nantes University, France; Hematology Department, CHU, Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*
chemical_list: D015703:Antigens, CD