From the Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to to: Andreas Mackensen, MD, Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen, Krankenhausstraße12, D-91054 Erlangen, Germany; e-mail: andreas.mackensen{at}uk-erlangen.de
Overview: The ability to adoptively transfer T cells to treat cancer has been demonstrated in animal models, but the task of translating the principles into the clinic has not been easy. A notable achievement in adoptive T-cell therapy was its use to treat viral infections, Epstein-Barr virus-associated lymphoma, and relapse of hematologic diseases after allogeneic bone marrow transplants. The persistence of adoptively transferred T cells and reconstitution of virus-specific immunity was demonstrated in the absence of noticeable side effects. The molecular characterization of tumor-associated antigens (TAA) has allowed the development of methods for the isolation and expansion of tumor-reactive T cells in vitro. This was a logical beginning for clinical application of targeted T-cell therapy. Recent studies have shown the efficacy of adoptive T-cell transfer therapies for the treatment of patients with metastatic melanoma. Effective cell therapy demands in vivo expansion of the transferred TAA-reactive T cells and homing to the tumor. Several strategies are being developed for enhancing the proliferation, migration, and persistence of infused tumor-reactive T cells, and for manipulating the host environment to eliminate regulatory cells, suppress inhibitory molecules, and to create space for expansion of the transferred cells. These approaches may improve the efficacy of adoptive T-cell therapy for cancer.
