Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells.
Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, and efficacy of adoptively transferred CD8+ T cell clones targeting the tumor-associated antigens, MART1MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 x 10(6) unitsm(2) twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1MelanA-specific or gp100-specific CD8+ T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persist in vivo in response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.
Yee
C
C
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109, USA. cyee@fhcrc.org
Thompson
J A
JA
Byrd
D
D
Riddell
S R
SR
Roche
P
P
Celis
E
E
Greenberg
P D
PD
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006085:Graft Survival; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D012008:Recurrence; D012449:Safety; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase