The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination.
An ideal vaccination strategy against tumors relies on specific antigens that are required for tumor maintenance. For lymphoma, vaccination with subject-specific immunoglobulin idiotypes has had the most promising results. Here we show that DNA vaccination with plasmids encoding portions of the cytoplasmic domain of anaplastic lymphoma kinase (ALK), which has been translocated in different fusion proteins necessary for the growth of anaplastic large cell lymphoma (ALCL), protects mice from local and systemic lymphoma growth. The protection is potent and long lasting and elicits ALK-specific interferon-gamma responses and CD8+ T cell-mediated cytotoxicity. A combination of chemotherapy and vaccination significantly enhanced the survival of mice challenged with ALK+ lymphomas. These findings indicate that ALK represents an ideal tumor antigen for vaccination-based therapies of ALCL and possibly other ALK+ human tumors.
Chiarle
Roberto
R
Center for Experimental Research and Medical Studies, University of Torino, Via Santena 7, 10126 Torino, Italy. roberto.chiarle@unito.it
Martinengo
Cinzia
C
Mastini
Cristina
C
Ambrogio
Chiara
C
D'Escamard
Valentina
V
Forni
Guido
G
Inghirami
Giorgio
G
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes / Q000378:metabolism; D007117:Immunization, Secondary; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases; D014611:Vaccination
D000951:Antigens, Neoplasm; D005456:Fluorescent Dyes; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D016650:Fluorescein-5-isothiocyanate