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Treatment of B cells malignancies with anti-CD19 CAR+, TCR-, CD52- allogeneic T cells
  1. Cécile Schiffer Mannioui1,
  2. Laëtitia Lemaire1,
  3. Laurent Poirot1,
  4. Agnes Gouble1,
  5. Sylvain Arnould1,
  6. Roman Galetto1,
  7. Julianne Smith1 and
  8. Andrew Scharenberg1
  1. Aff1 Cellectis Therapeutics Paris France

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Meeting abstracts

Encouraging data have emerged from adoptive T-cell therapies in advanced forms of cancer. Anti-tumor immunity is found in tumor infiltrating lymphocytes as well as engineered T cells where exogenous expression of a chimeric antigen receptor (CAR) confers cancer recognition on the cells. Present adoptive immunotherapy methods are restricted to the use of autologous patient T-cells due to the limited persistence of allogeneic T cells and the potential for graft versus host disease (GvHD). The use of autologous patient T cells in cancer immunotherapy is however limited due to the fact that this approach is complex and time consuming. We propose a novel approach to treat B cell malignancies based on the use of genetically modified allogeneic T cells in conjunction with the conditioning regimen alemtuzumab. Allogeneic T cells were engineered to express an anti-CD19 CAR and to no longer express TCRalpha and CD52, responsible for GVHD and the sensitivity to alemtuzumab, respectively. The inactivation of the TCRalpha and CD52 genes in allogeneic T cells was realized by using TALENTM, a novel class of sequence-specific nucleases created by the fusion of transcription activator-like effectors (TALEs) to the catalytic domain of an endonuclease. We have shown that anti-CD19 CAR+ TCR- CD52- allogeneic T cells did not respond to TCR stimulation, were resistant to alemtuzumab treatment and were able to kill target cells expressing CD19 in vitro and in vivo.