title: T cell-based targeted immunotherapies for patients with multiple myeloma.
abstract: Despite high-dose chemotherapy followed by autologs stem-cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression-free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect strongly supporting the usefulness of immunological therapies for MM patients. How to induce a powerful antimyeloma effect is the key issue in this field. Pivotal is the definition of appropriate tumor antigen targets and effective methods for expansion of T cells with clinical activity. Besides a comprehensive list of tumor antigens for T cell-based approaches, eight promising antigens, CS1, Dickkopf-1, HM1.24, Human telomerase reverse transcriptase, MAGE-A3, New York Esophageal-1, Receptor of hyaluronic acid mediated motility and Wilms' tumor gene 1, are described in detail to provide a background for potential clinical use. Results from both closed and on-going clinical trials are summarized in this review. On the basis of the preclinical and clinical data, we elaborate on three encouraging therapeutic options, vaccine-enhanced donor lymphocyte infusion, chimeric antigen receptors-transfected T cells as well as vaccines with multiple antigen peptides, to pave the way towards clinically significant immune responses against MM.
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, University of Heidelberg, Germany.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Jin
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Georg
authors.initials: G
authors.lastname: Malcherek
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
authors.forename: Jiju
authors.initials: J
authors.lastname: Mani
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Marc S
authors.initials: MS
authors.lastname: Raab
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm
keywords: clinical trials; genetic engineering; immunotherapy; multiple myeloma; tumor antigens