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

20 Citations (Scopus)

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

Fingerprint

Stem Cell Transplantation
Non-Hodgkin's Lymphoma
T-Lymphocytes
Bispecific Antibodies
Chemokine CCL4
Monokines
Macrophage Inflammatory Proteins
Interleukin-15
Interleukin-7
Chills
Immunosorbents
Antibodies
Natural Killer Cells
Hypotension
Fatigue
Immunity
Lymphoma
Fever
Drug Therapy

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

CD20-targeted T cells after stem cell transplantation for high risk and refractory non-hodgkin's lymphoma. / Lum, Lawrence G.; Thakur, Archana; Liu, Qin; Deol, Abhinav; Al-Kadhimi, Zaid; Ayash, Lois; Abidi, Muneer H.; Pray, Cassara; Tomaszewski, Elyse N.; Steele, Patricia A.; Schalk, Dana L.; Yano, Hiroshi; Mitchell, Alice; Dufresne, Melissa; Uberti, Joseph P.; Ratanatharathorn, Voravit.

In: Biology of Blood and Marrow Transplantation, Vol. 19, No. 6, 01.06.2013, p. 925-933.

Research output: Contribution to journalArticle

Lum, LG, Thakur, A, Liu, Q, Deol, A, Al-Kadhimi, Z, Ayash, L, Abidi, MH, Pray, C, Tomaszewski, EN, Steele, PA, Schalk, DL, Yano, H, Mitchell, A, Dufresne, M, Uberti, JP & 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, vol. 19, no. 6, pp. 925-933. https://doi.org/10.1016/j.bbmt.2013.03.010
Lum, Lawrence G. ; Thakur, Archana ; Liu, Qin ; Deol, Abhinav ; Al-Kadhimi, Zaid ; Ayash, Lois ; Abidi, Muneer H. ; Pray, Cassara ; Tomaszewski, Elyse N. ; Steele, Patricia A. ; Schalk, Dana L. ; Yano, Hiroshi ; Mitchell, Alice ; Dufresne, Melissa ; Uberti, Joseph P. ; Ratanatharathorn, Voravit. / CD20-targeted T cells after stem cell transplantation for high risk and refractory non-hodgkin's lymphoma. In: Biology of Blood and Marrow Transplantation. 2013 ; Vol. 19, No. 6. pp. 925-933.
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AU - Al-Kadhimi, Zaid

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AU - Abidi, Muneer H.

AU - Pray, Cassara

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