Generation of tumor-specific T lymphocytes for the treatment of posttransplant lymphoma

J. M. DiMaio, P. Van Trigt, J. W. Gaynor, R. D. Davis, E. Coveney, B. M. Clary, H. K. Lyerly

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: The incidence of lymphoproliferative disease, including B- cell lymphomas (BCL) in patients who have undergone heart or combined heart- lung transplants, has been reported to be as high as 15%. The majority of these tumors contain Epstein-Barr virus (EBV) DNA and regress when immunosuppressive agents are discontinued. This tumor regression is thought to be secondary to cytotoxic T lymphocytes (CTL) reactive to EBV-infected cells whose function is impaired in patients receiving immunosuppressive agents. We hypothesize that EBV-CTL expanded in the absence of these agents may demonstrate an antitumor effect against an EBV-expressing human BCL in vitro and in vivo. Methods and Results: An EBV-expressing BCL from a heart transplant recipient was isolated and expanded in culture. EBV-CTL were generated by stimulation of peripheral blood leukocytes with irradiated autologous tumor culls in low-dose interleukin-2. Autologous BCL, HLA- mismatched BCL, lymphokine-activated killer target cell line (Daudi), and the natural killer target cell line (K562) were used in a standard 4-hour cytotoxicity assay using 51CrO4 after 7, 14, and 28 days of stimulation. There was significant percent specific lysis of autologous BCL targets (78%) at all effector-to-target ratio as low as 20:1 as compared with control cells. EBV-CTL were then adoptively transferred into SCID mice (provided by Duke University Vivarium) that had been engrafted with autologous BCL 7 days before. There was a significant survival advantage to those mice engrafted with EBV-CTL as compared with control cells. Conclusions: The results indicate that ex vivo expansion of EBV-CTL in the absence of immunosuppressive agents results in a population that has significant antitumor activity. This strategy may be useful in the generation of EBV-CTL that might be effective antitumor agents in transplant recipients with EBV- associated lymphomas.

Original languageEnglish (US)
Pages (from-to)II202-II205
JournalCirculation
Volume92
Issue number9 SUPPL.
StatePublished - Jan 1 1995

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Keywords

  • cells
  • heart transplant
  • immunodeficiency
  • lymphocytes
  • lymphoma
  • transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

DiMaio, J. M., Van Trigt, P., Gaynor, J. W., Davis, R. D., Coveney, E., Clary, B. M., & Lyerly, H. K. (1995). Generation of tumor-specific T lymphocytes for the treatment of posttransplant lymphoma. Circulation, 92(9 SUPPL.), II202-II205.