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Pharmacol Res. 2014 Jan;79:9-12. doi: 10.1016/j.phrs.2013.10.004. Epub 2013 Nov 4.

Control of minimal residual cancer by low dose ipilimumab activating autologous anti-tumor immunity.

Author information

1
International Center for Cell Therapy and Cancer Immunotherapy (CTCI), 14 Weizman St., Tel Aviv 64238, Israel. Electronic address: slavin@CTCIcenter.com.
2
Cancer Decisions, PO Box 1076, Lemont, PA 16851, United States. Electronic address: ralphwmoss@gmail.com.
3
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.

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.

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

PMID:
24200897
DOI:
10.1016/j.phrs.2013.10.004
[Indexed for MEDLINE]

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