Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients.
Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.
Kim
D K
DK
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77035, USA.
Lee
T V
TV
Castilleja
A
A
Anderson
B W
BW
Peoples
G E
GE
Kudelka
A P
AP
Murray
J L
JL
Sittisomwong
T
T
Wharton
J T
JT
Kim
J W
JW
Ioannides
C G
CG
D001943:Breast Neoplasms / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011956:Receptors, Cell Surface; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface