Blood Journal
Leading the way in experimental and clinical research in hematology

Redirected tumor-specific allogeneic T cells for universal treatment of cancer

  1. Assaf Marcus,
  2. Tova Waks, and
  3. Zelig Eshhar*
  1. 1 Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
  1. * Corresponding author; email: zelig.eshhar{at}


Adoptive cell transfer of allogeneic tumor-specific T cells could potentially be used as a universal treatment for cancer. We present a novel approach for adoptive immunotherapy using fully MHC mismatched allogeneic T cells redirected with tumor-specific, non-MHC restricted antibody-based chimeric antigen receptor ("T-bodies") in the absence of graft versus host disease. Mice bearing systemic metastatic disease were lymphodepleted by irradiation and treated with Her2/neu redirected T cells. Lymphodepletion created a 'therapeutic window', which allowed the allo-T-bodies to attack the tumor before their rejection. A single split dose administration of allogeneic T-bodies extended the survival of tumor-bearing mice similarly to syngeneic T-bodies, and to a significantly greater extent than non-specific allogeneic T cells. Blocking egress of lymphocytes from lymphoid organs using the sphingosine-1-phosphate agonist, FTY720, extended the persistence of allogeneic T cells such that allogeneic T-bodies provided superior therapeutic benefit relative to syngeneic ones, and dramatically extended the median survival time of the treated mice for over a year. Therefore, we suggest that ex-vivo generated MHC-mismatched T-bodies can be used universally for 'off-the-shelf' cancer immunotherapy and that their graft versus host reactivity can be safely harnessed to potentiate adoptive cell therapy.

  • Submitted February 3, 2011.
  • Accepted May 6, 2011.