title: Old-School Chemotherapy in Immunotherapeutic Combination in Cancer, A Low-cost Drug Repurposed.
abstract: Cancer immunotherapy has proven to be a potent treatment modality. Although often successful in generating antitumor immune responses, cancer immunotherapy is frequently hindered by tumor immune-escape mechanisms. Among immunosuppressive strategies within the tumor microenvironment, suppressive immune regulatory cells play a key role in promoting tumor progression through inhibiting the effector arm of the immune response. Targeting these suppressive cells can greatly enhance antitumor immune therapies, hence augmenting a highly effective therapeutic antitumor response. Several approaches are being tested to enhance the effector arm of the immune system while simultaneously inhibiting the suppressor arm. Some of these approaches are none other than traditional drugs repurposed as immune modulators. Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. Preclinical and clinical findings have confirmed the ability of low doses of cyclophosphamide to selectively deplete regulatory T cells while enhancing effector and memory cytotoxic T cells within the tumor microenvironment. These immune effects translate to suppressed tumor growth and enhanced survival, evidence of antitumor therapeutic efficacy. This article discusses the reincarnation of cyclophosphamide as an immune modulator that augments novel immunotherapeutic approaches. Cancer Immunol Res; 4(5); 377-82. ©2016 AACR.
authors.affiliation: Georgia Cancer Center, Augusta University (Previously Georgia Regents University), Augusta, Georgia.
authors.forename: Rasha
authors.initials: R
authors.lastname: Abu Eid
authors.affiliation: Georgia Cancer Center, Augusta University (Previously Georgia Regents University), Augusta, Georgia.
authors.forename: Ghazaleh Shoja E
authors.initials: GS
authors.lastname: Razavi
authors.affiliation: Georgia Cancer Center, Augusta University (Previously Georgia Regents University), Augusta, Georgia.
authors.forename: Mikayel
authors.initials: M
authors.lastname: Mkrtichyan
authors.affiliation: Georgia Cancer Center, Augusta University (Previously Georgia Regents University), Augusta, Georgia.
authors.forename: John
authors.initials: J
authors.lastname: Janik
authors.affiliation: Georgia Cancer Center, Augusta University (Previously Georgia Regents University), Augusta, Georgia. SKHLEIF@gru.edu.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D058492:Drug Repositioning / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D003520:Cyclophosphamide