Identification of CD19 and CD20 peptides for induction of antigen-specific CTLs against B-cell malignancies.
The purpose of these studies was to develop immunogenic peptides derived from the CD19 and CD20 self-antigens for the induction of antigen-specific CTLs against B-cell malignancies. A total of seven peptides were designed and examined for their HLA-A2.1 affinity and immunogenicity. Of these peptides, we identified two highly immunogenic HLA-A2.1-specific peptides, CD19(150-158) (KLMSPKLYV) and CD20(188-196) (SLFLGILSV), which were capable of inducing peptide-specific CTLs. The CTLs displayed HLA-A2.1-restricted and antigen-specific cytotoxicity against Burkitt's lymphoma, chronic B cell leukemia, and multiple myeloma cell lines. The CD19 or CD20 peptide-specific CTL cytotoxicity was confirmed using HLA-A2.1(+) T2 cells presenting the appropriate peptide. No cytotoxic activity was observed against T2 cells presenting the irrelevant MAGE-3 peptide or T2 cells alone. In addition, the CTLs displayed a significant (P < 0.05) increase in cell proliferation and IFN-gamma secretion (>830 ng/mL) following restimulation with HLA-A2.1(+)/CD19(+)/CD20(+) tumor cells. The CTLs also displayed a distinct phenotype consisting of a high percentage of CD69(+)/CD45RO(+) and a low percentage of CD45RA(+)/CCR7(+) CD4(+) or CD8(+) T cells characteristic of effector memory cell population. Cyclic guanosine 3',5'-monophosphate culture conditions using serum-free AIM-V medium containing human AB serum, recombinant human interleukin 2 (Proleukin) and CD3/CD28 Dynabeads were developed resulting in a 35-fold expansion of CD20 peptide-specific CTLs. The expanded CD20-CTLs retained their cytotoxic activity (28-49%) against the Burkitt's lymphoma cell line. In conclusion, we report here on the identification of novel immunogenic CD19(150-158) (KLMSPKLYV) and CD20(188-196) (SLFLGILSV) peptides that have immunotherapeutic potentials as peptide vaccines or targeted T-cell therapies for treating B-cell malignancies.
Bae
Jooeun
J
Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL, USA. jooeum_bae@dfci.harvard.edu
Martinson
Jeffrey A
JA
Klingemann
Hans G
HG
D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000737:chemistry / Q000276:immunology; D018951:Antigens, CD20 / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells; D009842:Oligopeptides / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D018941:Antigens, CD19; D018951:Antigens, CD20; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D017464:Receptors, Complement 3d; D007371:Interferon-gamma