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

Lawrence 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

Research output: Contribution to journalArticle

23 Scopus citations

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 × 109. 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.

Original languageEnglish (US)
Pages (from-to)925-933
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Activated T cells
  • Autologous stem cell transplantation
  • Bispecific antibody
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Lum, L. G., Thakur, A., Liu, Q., Deol, A., Al-Kadhimi, Z., Ayash, L., Abidi, M. H., Pray, C., Tomaszewski, E. N., Steele, P. A., Schalk, D. L., Yano, H., Mitchell, A., Dufresne, M., Uberti, J. P., & Ratanatharathorn, V. (2013). CD20-targeted T cells after stem cell transplantation for high risk and refractory non-hodgkin's lymphoma. Biology of Blood and Marrow Transplantation, 19(6), 925-933. https://doi.org/10.1016/j.bbmt.2013.03.010