Adoptive cell therapy of systemic metastases using erbB-2-specifi c T cells redirected with a chimeric antibody-based receptor

Abstract

Immunotherapy of cancer using adoptive cell transfer combined with the advent of gene-engineering technologies has become an appealing option for a wide spectrum of cancers. In contrast to T cell receptor-based approaches, which are MHC restricted, chimeric antibody-based receptors (CAR), pioneered by our group, allow for a broader application, which are not restricted to individual tissue types. Here, we describe our studies using T cells redirected with CAR specifi c to the erbB-2 growth factor proto-oncogene as a common tumor target antigen. In a murine model for lung metastasis, we demonstrate that under defi ned conditions, CARexpressing T cells (T-bodies) can eliminate systemic lung metastases, which are generally felt to be incurable. The antitumor effect of systemically injected T-bodies was augmented by using increased injected cell doses and repeated administration cycles as well as by pre-vaccination of the tumor-bearing mice. Most importantly, we were able to establish a protocol enabling the use of MHC mismatched T-bodies in a safe and effective manner. We found that a single dose of allogeneic T-bodies under mild immunosuppressive conditions could cure metastases, demonstrating the effi cacy of this modality against disseminated disease. These results provide a proof of principle for using allogeneic erbB-2-specifi c T-bodies as a standard treatment of erbB-2-expressing tumors.