Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: a pilot study

Bone Marrow Transplant. 2014 Jan;49(1):73-9. doi: 10.1038/bmt.2013.133. Epub 2013 Sep 23.

Abstract

A pilot phase I clinical trial involving 15 infusions of anti-CD3 × anti-CD20 bispecific Ab (CD20Bi)-armed anti-CD3-activated T cells (aATC) and low-dose IL-2 was conducted in three non-Hodgkin's lymphoma (NHL) patients (two high-risk and one refractory) after autologous SCT. The feasibility of T-cell expansion, safety of aATC infusions, cytotoxic immune responses and trafficking of aATC were evaluated. Three NHL patients received 15 infusions of 5 × 10(9) aATC (three infusions/week for 3 weeks and one infusion/week for 6 weeks) between days 1 and 65 after SCT with IL-2. There were no dose-limiting toxicities. Chills, fever, hypotension and malaise were the common side effects. Engraftment was delayed in one patient with a low stem cell dose. CD20Bi aATC infusions induced specific cytotoxicity directed at lymphoma targets. Endogenous peripheral blood mononuclear cells from two patients mediated anti-lymphoma cytotoxicity above preSCT background (P<0.001). (111)In labeled aATC trafficked to the lungs at 1 h and accumulated in the liver and bone marrow after 24 h. aATC infusions given over 69 days in combination with IL-2 were safe, did not inhibit engraftment, and induced endogenous cytotoxic responses directed at lymphoma targets.

Publication types

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

MeSH terms

  • Aged
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD20 / metabolism
  • CD3 Complex / metabolism
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Immunophenotyping
  • Interleukin-2 / therapeutic use*
  • Leukapheresis
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Phenotype
  • Pilot Projects
  • Stem Cell Transplantation*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Bispecific
  • Antigens, CD20
  • CD20Bi antibody
  • CD3 Complex
  • Interleukin-2