Adoptive cell transfer is a promising treatment, with advances seen in patients with melanoma and neuroblastoma. The generation of tumor-specific T cells for patients, however, is technically and economically challenging. Zelig Eshhar and his team, who pioneered the use of redirected T cells with antibody-based non-MHC restricted chimeric antigen receptors, have developed a novel universal adoptive therapy approach for treating disseminated disease with no need for MHC matching between the donor cells and patient. Eshhar explains, “we hypothesized that low-dose irradiation would delay the host-versus-graft (HvG) effect allowing allogeneic T cells time to destroy the tumor, but that the allogeneic T cells would ultimately be rejected preventing graft-versus-host disease (GvHD).”
Mice with metastatic tumors were lymphodepleted by irradiation and treated with mismatched HER2 redirected T cells. The lymphocyte-sequestering agent, FTY720, allowed the HvG and graft-versus-host (GvH) responses to be inhibited to a far greater extent than graft-versus-tumor response. This approach cured a significantly higher proportion of mice compared with syngeneic T cells, with a striking median survival time of over 1 year in mice treated with the novel therapy. Eshhar adds, “our work conclusively demonstrates that GvH exploited to enhance the response of allogeneic tumor-specific T cells does not cause GvHD.” Allogeneic adoptive therapy may become the treatment of choice as it provides greater efficacy and cost advantages, although clinical validation is needed.
ORIGINAL RESEARCH PAPER
Marcus, A. et al. Redirected tumor-specific allogeneic T cells for universal treatment of cancer. Blood doi:10.1182/blood-2011-02-334284
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Hutchinson, L. Novel approach for universal adoptive cell transfer therapy with improved outcome. Nat Rev Clin Oncol 8, 447 (2011). https://doi.org/10.1038/nrclinonc.2011.100
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DOI: https://doi.org/10.1038/nrclinonc.2011.100