A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients

Bae, Jooeun; Prabhala, Rao; Voskertchian, Annie; Brown, Andrew S.; Maguire, Craig; Richardson, Paul G.; Dranoff, Glen; Anderson, Kenneth C.; Munshi, Nikhil C.

doi:10.1038/leu.2014.159

Cited by 57 publications

(42 citation statements)

References 48 publications

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“…These previously identified XBP1/CD138/CS1 peptides, either individually or as a cocktail of four peptides, induced antigens-specific CTL with functional anti-tumor activities against HLA-A2 + MM cells. 10-12, 15, 16 …”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma

et al. 2017

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XBP1 (X-box binding protein 1), CD138 (Syndecan-1), and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and anti-tumor activities, evidenced by perforin upregulation, CD107a degranulation (cytotoxicity) and Th1 type cytokines (IFN-γ/IL-2/TNF-α) production in response to HLA-A24+ MM cells. The multipeptide-specific CTL included antigen-specific memory CD8+ T cells expressing both T cell activation (CD38, CD69) and immune checkpoints antigens (CTLA, PD1, LAG3, TIM3). These results provide the framework for a multipeptide vaccination therapy to induce tumor-specific CTL in HLA-A24 positive patients with myeloma and other cancers expressing these antigens.

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Section: Discussionmentioning

confidence: 99%

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma

et al. 2017

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“…These results suggest that this multipeptide cocktail has the potential to induce effective and durable memory MP-CTL in SMM patients. Therefore, findings provide the rationale for clinical evaluation of a therapeutic vaccine to prevent or delay progression of SMM to active disease [117].…”

Section: Mgus Smoldering Myeloma and Vaccinationmentioning

confidence: 99%

Vaccination of multiple myeloma: Current strategies and future prospects

Allegra

Penna

Innao

et al. 2015

Critical Reviews in Oncology/Hematology

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“…One strategy that has been evaluated to overcome this limitation is the use of multipeptide vaccines that would generate a polyclonal response. 23,27 However, the list of known shared antigens is limited and their immunogenicity is uncertain. As tumor-associated antigens are self in origin, potentially reactive high-affinity T cells with greatest efficacy are deleted by the thymus during development by central tolerance.…”

Section: Single Antigen Peptide-and Protein-based Vaccinesmentioning

confidence: 99%

Vaccine therapy in hematologic malignancies

Avigan

Rosenblatt

2018

Blood

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Immune-based therapy has emerged as a paradigm shift in cancer therapy with dramatic responses observed in previously incurable disease. Cancer vaccines are being developed to disrupt tumor-associated tolerance and activate and selectively expand tumor-specific lymphocytes within the native effector cell repertoire while maintaining immune-regulatory protection against autoimmunity. Although individual antigen approaches result in immune response with a suggestion of clinical effect in some settings, broader efficacy may be dependent on presentation of multiple antigens that capture clonal diversity presented in the context of functionally potent antigen-presenting cells. The use of whole cell-based strategies such as dendritic cell/tumor fusions have yielded provocative results in single-arm studies and are currently being explored in multicenter randomized trials. The posttransplant setting is a potentially promising platform for vaccination due to cytoreduction and relative depletion of inhibitory accessory cells fostering greater immune responsiveness. Integration of these efforts with other immunotherapeutic strategies and agents that target the tumor microenvironment is being studied in an effort to generate durable immunologic responses with clinically meaningful impact on disease.

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A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients

Cited by 57 publications

References 48 publications

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma

Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma

Vaccination of multiple myeloma: Current strategies and future prospects

Vaccine therapy in hematologic malignancies

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