Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells.
Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T-cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects. We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T-cell receptor and neomycin resistance gene. Transfected cells were immunophenotypically similar to CD8(+) effector cells and showed CD20-specific cytotoxicity in vitro. Seven patients received a total of 20 T-cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections. Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease. These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at www.clinicaltrials.gov as #NCT00012207.
Till
Brian G
BG
Clinical Research Division of the Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. tillb@fhcrc.org
Jensen
Michael C
MC
Wang
Jinjuan
J
Chen
Eric Y
EY
Wood
Brent L
BL
Greisman
Harvey A
HA
Qian
Xiaojun
X
James
Scott E
SE
Raubitschek
Andrew
A
Forman
Stephen J
SJ
Gopal
Ajay K
AK
Pagel
John M
JM
Lindgren
Catherine G
CG
Greenberg
Philip D
PD
Riddell
Stanley R
SR
Press
Oliver W
OW
D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000235:genetics*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D017710:Lymphocyte Transfusion / Q000379:methods; D020522:Lymphoma, Mantle-Cell / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism / Q000637:transplantation*; D014162:Transfection; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018951:Antigens, CD20