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CD20-targeted T cells after stem cell transplantation for high risk and refractory non-Hodgkin's lymphoma.

Abstract
A phase I trial of infusing anti-CD3 × anti-CD20 bispecific antibody (CD20Bi) armed activated T cells (aATC) was conducted in high-risk/refractory non-Hodgkin's lymphoma patients to determine whether aATC infusions are safe, affect immune recovery, and induce an antilymphoma effect. Ex vivo expanded ATC from 12 patients were armed with anti-CD20 bispecific antibody, cryopreserved, and infused after autologous stem cell transplantation (SCT). Patients underwent SCT after high-dose chemotherapy, and aATC infusions were started on day +4. The patients received 1 infusion of aATC per week for 4 weeks after SCT with doses of 5, 10, 15, and 20 × 10(9). aATC infusions were safe and did not impair engraftment. The major side effects were chills, fever, hypotension, and fatigue. The mean number of IFN-γ Enzyme-linked Immunosorbent Spots (ElSpots) directed at CD20 positive lymphoma cells (DAUDI, P = .0098) and natural killer cell targets (K562, P < .0051) and the mean specific cytotoxicity directed at DAUDI (P = .037) and K562 (P = .002) from pre-SCT to post-SCT were significantly higher. The increase in IFN-γ EliSpots from pre-SCT to post-SCT in patients who received armed ATC after SCT were significantly higher than those in patients who received SCT alone (P = .02). Serum IL-7, IL-15, Macrophage inflammatory protein (MIP)-1 beta, IP-10, MIP-1α, and Monokine induced by gamma interferone increased within hours after infusion. Polyclonal and specific antibodies were near normal 3 months after SCT. aATC infusions were safe and increased innate and specific antilymphoma cell immunity without impairing antibody recovery after SCT.
AuthorsLawrence G Lum, Archana Thakur, Qin Liu, Abhinav Deol, Zaid Al-Kadhimi, Lois Ayash, Muneer H Abidi, Cassara Pray, Elyse N Tomaszewski, Patricia A Steele, Dana L Schalk, Hiroshi Yano, Alice Mitchell, Melissa Dufresne, Joseph P Uberti, Voravit Ratanatharathorn
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 19 Issue 6 Pg. 925-33 (Jun 2013) ISSN: 1523-6536 [Electronic] United States
PMID23529012 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antibodies, Bispecific
  • Antigens, CD20
  • Antineoplastic Agents
  • CD3 Complex
  • Cytokines
Topics
  • Aged
  • Antibodies, Bispecific (therapeutic use)
  • Antigens, CD20 (genetics, immunology)
  • Antineoplastic Agents (therapeutic use)
  • CD3 Complex (genetics, immunology)
  • Cell Proliferation
  • Cytokines (biosynthesis, immunology)
  • Cytotoxicity, Immunologic
  • Female
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Killer Cells, Natural (immunology, pathology)
  • Lymphoma, Non-Hodgkin (immunology, pathology, therapy)
  • Middle Aged
  • T-Lymphocytes (immunology, transplantation)
  • Transplantation, Autologous
  • Treatment Failure

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