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Identification of CD19 and CD20 Peptides for Induction of Antigen-Specific CTLs against B-Cell Malignancies

Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, Illinois

Requests for reprints: Jooeun Bae, Department of Medical Oncology, Dana-Farber Cancer Institute/VA Hospital, Harvard Medical Center, 1400 VWF Parkway, Room 2A111, Building 3, West Roxbury, MA 02132. Phone: 617-323-7700 Ext. 6171; Fax: 617-363-5592; E-mail: jooeun_bae{at}dfci.harvard.edu.

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- 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.

Key Words: Hematological disorders • Self-antigen • Immunotherapy • Peptide-specific cytotoxic • T lymphocytes

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