4-1BB-based isolation and expansion of CD8+ T cells specific for self-tumor and non-self-tumor antigens for adoptive T-cell therapy.
Adoptive T-cell therapy is a promising approach to the immunotherapy of cancer, but for it to be a general cancer therapy a simple and standardized procedure for producing tumor-specific CD8 T cells is needed. On the basis of a unique property of 4-1BB (CD137), the selective expression on activated T cells, we have developed a simple and practical protocol to produce antigen-specific CD8 T cells from peripheral blood mononuclear cells. We have proved the feasibility of this procedure by isolating and expanding cytomegalovirus-specific CD8 T cells, and applied the procedure to produce Epstein-Barr virus (EBV)-specific CD8 T cells. By using this procedure, we could readily produce 10-10 antigen-specific CD8 T cells from 30 to 50 mL of blood in about 4 weeks. Moreover, our protocol allowed us to produce, from solid cancer patients, CD8 T cells that were specific for self/tumor antigens such as human telomerase reverse transcriptase (hTERT). It is interesting to note that, we were unable to amplify hTERT-specific CD8 T cells from healthy donors. Our protocol can be readily translated into cGMP-compliant production and is currently being used to produce EBV-specific CD8 T cells for phase I clinical trial. We believe that our method will provide a practical and effective option for adoptive T-cell therapy in the clinic.
*Immune & Cell Therapy Branch, Division of Cancer Biology ‡Biomedicine Production Branch §Center for Gastric Cancer, National Cancer Center, Goyang †Personalized Medicine System R&D Center, Bio-Support Co., Ltd, Gwanyang, Dongan, Anyang, Gyeonggi ∥Department of Surgery, Kosin University College of Medicine, Busan, Korea ¶T Cell Technologies Inc., Nagoya, Aichi, Japan #Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA.
Beom K
BK
Choi
Sang C
SC
Lee
Myoung J
MJ
Lee
Young H
YH
Kim
Young-Woo
YW
Kim
Keun-Won
KW
Ryu
Jun-Ho
JH
Lee
Su M
SM
Shin
Sang-Ho
SH
Lee
Susumu
S
Suzuki
Ho S
HS
Oh
Chang H
CH
Kim
Don G
DG
Lee
Sun H
SH
Hwang
Eun-Mi
EM
Yu
In O
IO
Lee
Byoung S
BS
Kwon
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010641:Phenotype; D010750:Phosphoproteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D019098:Telomerase / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D001324:Autoantigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D010750:Phosphoproteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D019098:Telomerase