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Autografting

Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: A pilot study

Bone Marrow Transplantation volume 49, pages 73–79 (2014)Cite this article

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Abstract

A pilot phase I clinical trial involving 15 infusions of anti-CD3 × anti-CD20 bispecific Ab (CD20Bi)-armed anti-CD3-activated T cells (aATC) and low-dose IL-2 was conducted in three non-Hodgkin’s lymphoma (NHL) patients (two high-risk and one refractory) after autologous SCT. The feasibility of T-cell expansion, safety of aATC infusions, cytotoxic immune responses and trafficking of aATC were evaluated. Three NHL patients received 15 infusions of 5 × 109 aATC (three infusions/week for 3 weeks and one infusion/week for 6 weeks) between days 1 and 65 after SCT with IL-2. There were no dose-limiting toxicities. Chills, fever, hypotension and malaise were the common side effects. Engraftment was delayed in one patient with a low stem cell dose. CD20Bi aATC infusions induced specific cytotoxicity directed at lymphoma targets. Endogenous peripheral blood mononuclear cells from two patients mediated anti-lymphoma cytotoxicity above preSCT background (P<0.001). 111In labeled aATC trafficked to the lungs at 1 h and accumulated in the liver and bone marrow after 24 h. aATC infusions given over 69 days in combination with IL-2 were safe, did not inhibit engraftment, and induced endogenous cytotoxic responses directed at lymphoma targets.

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Acknowledgements

LGL was supported in part by grants from the Leukemia and Lymphoma Society (TRP 6066–06), the National Cancer Institute R01 CA 092344 and the Raymond Neag Foundation. AD was supported in part by startup funding from the Department of Oncology, Wayne State University. We acknowledge the efforts of clinical coordinators and nurse practitioners, Wendy Young, Annette Olson, Janet McIntyre and Lori Hall, who took a special interest in coordinating patient care, follow-up and monitoring infusions.

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  1. L G Lum and A Thakur: Equal first author contributions

Authors and Affiliations

  1. Department of Oncology, Wayne State University, Detroit, MI, USA

    L G Lum, A Thakur, C Pray & A Deol

  2. Department of Medicine, Wayne State University, Detroit, MI, USA

    L G Lum & A Deol

  3. Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA

    L G Lum

  4. Roger Williams Medical Center, Providence, RI, USA

    N Kouttab, W M Colaiace & R Rathore

  5. Department of Medicine, University of California, Davis, Sacramento, CA, USA

    M Abedi

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Correspondence to L G Lum.

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Dr Lum is co-founder of Transtarget, Inc. The other authors declare no conflict of interest

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Lum, L., Thakur, A., Pray, C. et al. Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: A pilot study. Bone Marrow Transplant 49, 73–79 (2014). https://doi.org/10.1038/bmt.2013.133

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