Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells

Blood. 2008 Sep 15;112(6):2261-71. doi: 10.1182/blood-2007-12-128843. Epub 2008 May 28.

Abstract

Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T-cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects. We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T-cell receptor and neomycin resistance gene. Transfected cells were immunophenotypically similar to CD8(+) effector cells and showed CD20-specific cytotoxicity in vitro. Seven patients received a total of 20 T-cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections. Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease. These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at www.clinicaltrials.gov as #NCT00012207.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antigens, CD20 / genetics*
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Transfusion / methods
  • Lymphoma, Mantle-Cell / therapy*
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Remission Induction
  • Salvage Therapy / methods
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Transfection
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Antigens, CD20

Associated data

  • ClinicalTrials.gov/NCT00012207