Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.
Increasing evidence suggests that adoptive transfer of antigen-specific CD8(+) T cells could represent an effective strategy in the fight against chronic viral infections and malignancies such as melanoma. None the less, a major limitation in the implementation of such therapy resides in the difficulties associated with achieving rapid and efficient expansion of functional T cells in culture necessary to obtain the large numbers required for intravenous infusion. Recently, the critical role of the cytokines interleukin (IL)-2, IL-7 and IL-15 in driving T cell proliferation has been emphasized, thus suggesting their use in the optimization of expansion protocols. We have used major histocompatibility complex (MHC) class I/peptide multimers to monitor the expansion of antigen-specific CD8 T lymphocytes from whole blood, exploring the effect of antigenic peptide dose, IL-2, IL-7 and IL-15 concentrations on the magnitude and functional characteristics of the antigen-specific CD8(+) T cells generated. We show here that significant expansions of antigen-specific T cells, up to 50% of the CD8(+) T cell population, can be obtained after a single round of antigen/cytokine (IL-2 or IL-15) stimulation, and that these cells display good cytolytic and interferon (IFN)-gamma secretion capabilities. Our results provide an important basis for the rapid in vitro expansion of autologous T cells from the circulating lymphocyte pool using a simple procedure, which is necessary for the development of adoptive transfer therapies.
Montes
M
M
Multidisciplinary Oncology Center (CePO), University Hospital (CHUV), Lausanne, Switzerland.
Rufer
N
N
Appay
V
V
Reynard
S
S
Pittet
M J
MJ
Speiser
D E
DE
Guillaume
P
P
Cerottini
J-C
JC
Romero
P
P
Leyvraz
S
S
D019264:Adoptive Transfer; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D018929:Cell Culture Techniques; D002455:Cell Division; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins