Adoptive transfer of tumor specific T cells from allogeneic donors is feasible, effective and safe alternative to autologous T cell based tumor immunotherapy

  • Eliza P. Kwiatkowska-Borowczyk Department of Cancer Immunology, Poznan University of Medical Sciences, Poland Diagnostic and Immunology Department, Greater Poland Cancer Centre, Poznan, Poland
  • Anna Kozłowska Department of Cancer Immunology, Poznan University of Medical Sciences, Poland
  • Klaudia Maruszak Department of Pathology, MSW Hospital, Olsztyn, Poland
  • Luiza Kańczuga-Koda Department of Pathology, MSW Hospital, Olsztyn, Poland
  • Mariusz Koda Department of Pathology, MSW Hospital, Olsztyn, Poland
  • Monika Dajnowiec Department of Pathophysiology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, Poland
  • Andrzej Mackiewicz Department of Cancer Immunology, Poznan University of Medical Sciences, Poland Diagnostic and Immunology Department, Greater Poland Cancer Centre, Poznan, Poland
  • Dariusz W. Kowalczyk Department of Pathophysiology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, Poland
Keywords: adoptive cell transfer, tumor immunotherapy, cancer, GVHD, allogeneic T cells, murine model

Abstract

Donor lymphocyte infusion is used to increase the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplant. The limited spectrum of activity and high risk of graft versus host disease (GVHD) remain major limitations of this approach. The finding of new cell populations for adoptive immunotherapy, with the ability to separate GVT from GVHD, would be useful. In the present manuscript, we tested in mouse model the use of allogeneic MHC partially matched effector cells for adoptive T cell immunotherapy of cancer. We sought to maximize graft-versus-tumor effect while minimizing GVHD using tumor-specific allogeneic effector T cells rather than open-repertoire T cells. A F1 hybrid (Balb/c x C57BL/6) -MethA-EGFP–bearing mice received a preparative regimen of nonmyeloablating cyclophosphamide lymphodepletion followed by adoptive transfer of bulk Balb/c derived allogeneic T cells specific for the MethA-EGFP tumor cells. Adoptively transferred allogeneic tumor-specific T lymphocytes prevented tumor formation without graft versus host disease – like symptoms. We found that the risk of GVHD was low even with high number of transferred tumor-specific T cells. These data indicate that the use of tumor-specific allogeneic T cells is feasible, effective and safe alternative to autologous T cell based tumor immunotherapy.