Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice

Blood Cancer J. 2016 Jun 3;6(6):e430. doi: 10.1038/bcj.2016.38.

Abstract

Despite the impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR-Ts), the current applications of CAR-T cell therapy are limited by major treatment-related toxicity. Thus, safer yet effective alternative approaches must be developed. In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both in vitro and in an aggressive Nalm6 leukemia mouse model. BiTEs were secreted from the transferred T cells and enabled both the transferred and bystander T cells to specifically recognize CD19(+) cell lines, with increased tumor killing ability, prolonged functional persistence, increased cytokine production and potent proliferation compared with the CAR-T cells. More interestingly, in comparison with CD3/CD28 bead-stimulated T cells, T cells that were expanded by a rapid T-cell expansion protocol (REP) showed enhanced anti-tumor activities for both CAR and BiTE RNA-electroporated T cells both in vitro and in a Nalm6 mouse model (P<0.01). Furthermore, the REP T cells with BiTE RNAs showed greater efficacy in the Nalm6 leukemia model compared with REP T cells with CAR RNA (P<0.05) and resulted in complete leukemia remission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • Cell Line, Tumor
  • Cell- and Tissue-Based Therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Leukemia / immunology*
  • Leukemia / pathology
  • Leukemia / therapy
  • Lymphocyte Activation / immunology
  • Mice
  • Oncogene Proteins, Fusion / genetics
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / transplantation
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD19
  • Oncogene Proteins, Fusion
  • Receptors, Antigen