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Tumor-Specific T Cells and Response in Relapsed Hodgkin Lymphoma

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Key Points

  • The DNRII LMP-specific T cells expanded and persisted for ≥ 4 years.
  • Complete response was achieved in four of seven patients, with response persisting ≥ 4 years in two.

In a study reported in the Journal of Clinical Oncology, Bollard et al found that T cells with forced expression of dominant-negative transforming growth factor-β (TGF-β) receptor type 2 (DNRII) that targeted the Epstein Barr virus (EBV)-derived tumor antigens latent membrane proteins (LMP)-1 and -2 (DNRII-LSTs) produced durable responses in patients with relapsed EBV-positive Hodgkin lymphoma.

TGF-β production in the tumor microenvironment is a tumor immune evasion mechanism that inhibits tumor-directed immune responses.

Study Details and Findings

In the dose-escalation study, 8 patients received 2 to 12 doses of between 2 x 107 and 1.5 x 108 cells/m2 of DNRII-LSTs. Lymphodepleting chemotherapy was not used before infusion.

The DNRII-LSTs were resistant to otherwise inhibitory TGF-β concentrations in vitro and retained tumor antigen-specific activity. Signals from the transgenic T-cells in peripheral blood increased up to 100-fold after infusion, and a corresponding increase in frequency of functional LMP-specific T cells was observed. The T cell expansion was not associated with acute or long-term toxicity.

The DNRII-LSTs persisted for up to ≥ 4 years. Clinical complete responses were observed in four of seven evaluable patients. In two, responses were ongoing at ≥ 4 years, including in one patient who had a partial response to unmodified tumor-directed T cells.

The investigators concluded, “TGF-β–resistant tumor-specific T-cells safely expand and persist in patients with Hodgkin lymphoma without lymphodepleting chemotherapy before infusion. DNRII-LSTs can induce complete responses even in patients with resistant disease. Expression of DNRII may be useful for the many other tumors that exploit this potent immune evasion mechanism.”

The study was supported by grants from the National Institutes of Health and Leukemia and Lymphoma Society.

Catherine M. Bollard, MD, of the Center for Cancer and Immunology Research, Children’s National Health System, The George Washington University, is the corresponding author for the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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