| Literature DB >> 24200897 |
Shimon Slavin1, Ralph W Moss2, Tibor Bakacs3.
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.Entities:
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
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Year: 2013 PMID： 24200897 DOI： 10.1016/j.phrs.2013.10.004
Source DB: PubMed Journal: Pharmacol Res ISSN： 1043-6618 Impact factor: 7.658