scholarly journals Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma

Leukemia ◽  
2011 ◽  
Vol 25 (10) ◽  
pp. 1610-1619 ◽  
Author(s):  
J Bae ◽  
R Carrasco ◽  
A-H Lee ◽  
R Prabhala ◽  
Y-T Tai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Therapeutic Application ◽  
Potential Therapeutic Application

Novel Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: Potential Therapeutic Application in Multiple Myeloma and Other Plasma Cell Disorders,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3990-3990
Author(s):  
Jooeun Bae ◽  
Ruben Carrasco ◽  
Ann-Hwee Lee ◽  
Rao Prabhala ◽  
Yu-Tzu Tai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Board Of Directors ◽  
Cytotoxic T Lymphocytes ◽  
Plasma Cell ◽  
Peptide Vaccine ◽  
Effector Memory ◽  
Therapeutic Application ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Abstract 3990 Although single antigen targeted vaccination has been evaluated in multiple myeloma (MM), its efficacy has been limited. The major challenges in developing a MM-specific immunotherapy include heterogeneity of tumor associated antigens (TAA) expression, frequent mutations of specific TAA and variability of the human T-cell repertoire. We hypothesize that peptide vaccine efficacy may be enhanced by stimulating immune cells with multiple epitopes derived from different TAA. The goal of our study was to examine the effectiveness of a combination of four immunogenic HLA-A2-specific peptides derived from multiple MM-associated antigens to induce myeloma-specific cytotoxic T lymphocytes (CTL) ex vivo. The specific target antigens, XBP1, CD138 and CS1 play a significant role in MM pathogenesis. We have identified immunogenic HLA-A2-specific epitopes: heteroclitic XBP1 US184–192 (YISPWILAV), heteroclitic XBP1 SP367–375 (YLFPQLISV), native CD138260–268(GLVGLIFAV) and native CS1239–247 (SLFVLGLFL). In this study, first we evaluated each of the four epitopes in parallel and confirmed strong HLA-A2 binding affinity of the four individual peptides and demonstrated comparable phenotypes and overall functional activity of CTL generated with each peptide against HLA-A2+ MM cells. We next evaluated the multipeptide-specific CTL (MP-CTL) generated using a combination of all four peptides. The MP-CTL had an increased percentage of total CD8+ T cells, CCR7−CD45RO+(effector memory) and CD69+ (activated) cells. In addition, the MP-CTL demonstrated polyfunctional immune activities [higher IFN-g production, cell proliferation and cytotoxicity] against HLA-A2+ primary MM cells and MM cell lines, but not to HLA-A2− MM cells or HLA-A2+ breast cancer cells. Importantly, the MP-CTL demonstrated peptide-specific responses to all relevant epitopes including heteroclitic XBP1 US184–192 (YISPWILAV), heteroclitic XBP1 SP367–375 (YLFPQLISV), native CD138260–268(GLVGLIFAV) and native CS1239–247 (SLFVLGLFL), but not to an irrelevant CMV pp65 (NLVPMVATV) peptide in a various functional assays evaluated cytokine production and cytotoxicity. Moreover, the MP-CTL demonstrated similar or greater response against MM, compared to CTL generated using the individual peptides. Thus, targeting MM-associated antigens using a cocktail of specific peptides may provide an effective therapeutic application in patients with MM and related plasma cell disorders. Disclosures: Anderson: Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Munshi:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Lenalidomide Augments the Antitumor Activities of Eps8 Peptide-Specific Cytotoxic T Lymphocytes against Multiple Myeloma

2019 ◽  
Vol 18 (12) ◽  
pp. 2258-2269 ◽  
Author(s):  
Xiaoling Xie ◽  
Yiran Chen ◽  
Yuxing Hu ◽  
Yanjie He ◽  
Honghao Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Antitumor Activities

Induction of Multiple Myeloma-Specific Cytotoxic T Lymphocytes Using HLA-A2.1-Specific CD19 and CD20 Peptides.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2477-2477
Author(s):  
Jooeun Bae ◽  
Jeff A. Martinson ◽  
Hans G. Klingemann ◽  
Steven Treon ◽  
Kenneth C. Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cytotoxic T Lymphocytes ◽  
Myeloma Cell ◽  
Myeloma Cells ◽  
Specific Ctls ◽  
Ifn Γ ◽  
Hla A2.1

Abstract We have identified novel CD19 and CD20 antigen-derived HLA-A2.1-specific immunogenic peptides, CD19150–158 (KLMSPKLYV) and CD20188–196 (SLFLGILSV), for generating cytotoxic T lymphocytes (CTLs) against malignant B-cell diseases. Initial testing showed that the CTLs displayed antigen-specific and HLA-A2.1-restriced cytotoxic activity against both Burkitt’s lymphoma and chronic lymphoid leukemia cell lines. The observed cytotoxic activity of the CTLs was shown to be specific to the CD19150–158 or the CD20188–196 peptides. Additionally, the CTLs displayed a distinct phenotype (majority CD69+/CD45RO+) along with a significant (p<0.05) increase in cell proliferation and IFN-γ release following re-stimulation with HLA-A2.1+/CD19+/CD20+ tumor cell lines. Based on emerging information that clonogenic myeloma cells express CD19 and/or CD20, we evaluated the activity of the CD19 and CD20 peptide specific-CTLs against several multiple myeloma cell lines. Five of 10 myeloma cell lines evaluated were HLA-A2.1-positive and expressed both CD19 and CD20 antigens. CD19 peptide specific-CTLs generated from normal donors were able to specifically lyse CD19+/HLA-A2.1+ MM cell lines (30% lysis; 10:1 E:T ratio) but did not lyse CD19−/HLA-A2.1+ or CD19+/HLA-A2.1− cell lines. Similarly, the CD20-specific CTLs generated from normal donors lysed CD20+/HLA-A2.1+ MM cell lines (25% lysis; 10:1 E:T ratio), in a manner restricted to HLA-A2.1 and specific to antigens. We next showed IFN-γ production by the CTLs after exposure to CD19+/HLA-A2.1+ or CD20+/HLA-A2.1+ MM cells. Moreover, we have demonstrated the ability to expand CD20-CTLs under serum-free culture conditions while maintaining their cytotoxic activity (28–49%). In ongoing studies, we are evaluating the ability of CD19- and CD20-specific CTLs to eliminate clonogenic myeloma cells in vitro and in vivo in a SCID mouse model of myeloma. These preclinical studies strongly suggest that immunogenic CD19 and CD20 peptide-based vaccines represent a promising immunotherapeutic approach in myeloma.

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