title: Control of minimal residual cancer by low dose ipilimumab activating autologous anti-tumor immunity.
abstract: In this perspective article, we address the controversy regarding the safety-efficacy issue in ipilimumab trials. While the CTLA-4 blockade interrupted T-cell pathways responsible for immune down-regulation and mediated regression of established malignant tumors in a minority of patients, this has to be weighed against the immune related adverse events (irAEs) suffered by the majority. Based on two groundbreaking but neglected proof-of-principle papers that demonstrated augmented graft-vs.-malignancy (GVM) effect that reversed the relapse of malignancy without worsening the graft-vs.-host disease (GVHD) by a CTLA-4 blockade, here we suggest a therapeutic paradigm shift, which may help break the impasse and resolve this timely issue in oncology.
authors.affiliation: International Center for Cell Therapy and Cancer Immunotherapy (CTCI), 14 Weizman St., Tel Aviv 64238, Israel. Electronic address: slavin@CTCIcenter.com.
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.affiliation: Cancer Decisions, PO Box 1076, Lemont, PA 16851, United States. Electronic address: ralphwmoss@gmail.com.
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Moss
authors.affiliation: Department of Probability, Alfred Renyi Institute of Mathematics, Hungarian Academy of Sciences, Realtanoda utca 13-15, H-1053 Budapest, Hungary. Electronic address: tiborbakacs@gmail.com.
authors.forename: Tibor
authors.initials: T
authors.lastname: Bakacs
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015551:Autoimmunity; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D006086:Graft vs Host Disease; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D018365:Neoplasm, Residual / Q000276:immunology / Q000628:therapy; D033581:Stem Cell Transplantation
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab
keywords: Anti-cancer immunotherapy; Autoimmunity; Autologous and allogeneic graft-vs.-host disease (GVHD); CTLA-4; CTLA-4 blockade; DLI; GVHD; GVL; GVM; Graft-vs.-leukemia (GVL) effects; Graft-vs.-malignancy (GVM) effects; Homeostatic proliferation; Ipilimumab; MHC; MRD; Minimal residual disease (MRD); SCT; Self and alloreactive T cells; T cell receptor; TCR; Treg; cytotoxic T lymphocyte-associated antigen-4; donor lymphocyte infusion; graft-vs.-host disease; graft-vs.-leukemia effects; graft-vs.-malignancy; immune-related adverse events; irAEs; mAbs; major histocompatibility complex; minimal residual disease; monoclonal antibodies; regulatory T cells; stem cell transplantation