Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: a pilot study.
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 × 10(9) 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). (111)In 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.
1] Department of Oncology, Wayne State University, Detroit, MI, USA [2] Department of Medicine, Wayne State University, Detroit, MI, USA [3] Department of Immunology and Microbiology, Wayne State University, Detroit, MI, USA.
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Lum
Department of Oncology, Wayne State University, Detroit, MI, USA.
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Thakur
Department of Oncology, Wayne State University, Detroit, MI, USA.
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Pray
Roger Williams Medical Center, Providence, RI, USA.
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Kouttab
Department of Medicine, University of California, Davis, Sacramento, CA, USA.
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Abedi
1] Department of Oncology, Wayne State University, Detroit, MI, USA [2] Department of Medicine, Wayne State University, Detroit, MI, USA.
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Deol
Roger Williams Medical Center, Providence, RI, USA.
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Colaiace
Roger Williams Medical Center, Providence, RI, USA.
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Rathore
D000368:Aged; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000627:therapeutic use*; D007937:Leukapheresis; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018033:Antibodies, Bispecific; D018951:Antigens, CD20; C000591163:CD20Bi antibody; D017252:CD3 Complex; D007376:Interleukin-2