Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals.
Although high frequencies of T lymphocytes specific for certain tumor-associated antigens have been detected in some cancer patients, increasing evidence suggests that these T cells may be functionally defective in vivo and fail to induce meaningful clinical responses. One strategy to overcome this limitation is to target novel antigens that are ignored during the natural antitumor immune response but are nevertheless capable of triggering effector T-cell responses against tumors after optimal presentation by antigen-presenting cells. Here, we show that the telomerase catalytic subunit (hTERT)-a nearly universal tumor antigen identified by epitope deduction rather than from patient immune responses-is immunologically ignored by patients despite progressive tumor burden. Nevertheless, HLA-A2-restricted CTLs against hTERT are equivalently induced ex vivo from patients and healthy individuals and efficiently kill human tumor cell lines and primary tumors. Thus, telomerase-specific T cells from cancer patients are spared functional inactivation because of immunological ignorance. These findings support clinical efforts to target the hTERT as a tumor antigen with broad therapeutic potential.
Vonderheide
R H
RH
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. rhv@mail.med.upenn.edu
Schultze
J L
JL
Anderson
K S
KS
Maecker
B
B
Butler
M O
MO
Xia
Z
Z
Kuroda
M J
MJ
von Bergwelt-Baildon
M S
MS
Bedor
M M
MM
Hoar
K M
KM
Schnipper
D R
DR
Brooks
M W
MW
Letvin
N L
NL
Stephans
K F
KF
Wucherpfennig
K W
KW
Hahn
W C
WC
Nadler
L M
LM
D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*
D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D019098:Telomerase