BCMA peptide-engineered nanoparticles enhance induction and function of antigen-specific CD8+ cytotoxic T lymphocytes against multiple myeloma: clinical applications

Bae, Jooeun; Parayath, Neha N.; Ma, Wenxue; Amiji, Mansoor M.; Munshi, Nikhil C.; Anderson, Kenneth C.

doi:10.1038/s41375-019-0540-7

Cited by 41 publications

(38 citation statements)

References 61 publications

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“…We identified P(BCMA) B*18 as a highly immunogenic naturally presented epitope capable of inducing potent and multifunctional cytotoxic T-cell responses. This is in line with recent data reporting on the high immunogenicity of computationally predicted HLA*02-restricted T-cell epitopes derived from the extracellular surface domain of BCMA 32,33 . Our mass spectrometric approach further allowed us to validate P(BCMA) B*18 additionally as a target for CLL, for which plasma BCMA-levels were described as a prognostic factor 34 .…”

Section: Discussionsupporting

confidence: 92%

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

et al. 2020

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The B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18restricted ligand P(BCMA) B*18. Additionally, P(BCMA) B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA) B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8 + T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA) B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA) B*18-specific CD8 + T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA) B*18 using patient-derived P(BCMA) B*18-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.

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Section: Discussionsupporting

confidence: 92%

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

et al. 2020

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“…At present, the main specific antigens of MM that show potential in the targeting therapy of MM include BCMA [ 90 ], HM1.24 [ 91 ], MUC-1 [ 92 ], MAGE-C1 [ 93 ], B7-H1 [ 94 ] and HSP [ 95 ]. To date, there has been no investigation reporting the application of DC-EXs in an anti-myeloma vaccine.…”

Section: The Roles Of Exosomes In Cancer Vaccinesmentioning

confidence: 99%

Recent Progress of Exosomes in Multiple Myeloma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Strategies

Wang

Huang

et al. 2021

Cancers

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Multiple myeloma (MM) is a hematological malignancy that is still incurable. The bone marrow microenvironment (BMM), with cellular and non-cellular components, can create a favorable environment for the survival, proliferation and migration of MM cells, which is the main reason for the failure of MM therapies. Many studies have demonstrated that exosomes play an important role in the tumor-supportive BMM. Exosomes are nanoscale vesicles that can be released by various cells. Some exosomes contribute to the pathogenesis and progression of MM. MM-derived exosomes act on different cells in the BMM, thereby creating an environment conducive to the survival and growth of MM cells. Owing to the important roles of exosomes in the BMM, targeting the secretion of exosomes may become an effective therapeutic strategy for MM. In addition, the abnormal expression of “cargos” in the exosomes of MM patients may be used to diagnose MM or used as part of a screen for the early prognoses of MM patients. Exosomes also have good biological properties, including safety, biocompatibility, stability and biodegradability. Therefore, the encapsulation of anti-cancer drugs in exosomes, along with surface modifications of exosomes with targeting molecules, are very promising strategies for cancer therapies—particularly for MM. In addition, DC-derived exosomes (DC-EXs) can express MHC-I, MHC-II and T cell costimulatory molecules. Therefore, DC-EXs may be used as a nanocarrier to deliver cancer vaccines in MM. This review summarizes the recent progress of exosome research regarding the pathogenesis of, diagnosis of, prognosis of and therapeutic strategies for MM.

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“…Possesses the influencing factors to immune responses and induces a systemic antigen specific immune response. [ 76 ] Poly(propylene) sulfide (PPS) CD4+ and CD8+ T-cell inducer, passive targeting of the lymph node. In the presence of ipsilateral, the PPS aims at TDLNs.…”

Section: Specific Delivery Of Immunotherapies From the Nanoparticle-imentioning

confidence: 99%

Enhancing Cancer Immunotherapy Treatment Goals by Using Nanoparticle Delivery System

Muluh¹,

Chen²,

Li³

et al. 2021

IJN

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Recently, there has been an incredible increase in research about the abnormal growth of cells (neoplasm), focusing on the management, treatment and preventing reoccurrence. It has been understood that the natural defense system, composed of a variety of immune defensive cells, does not just limit its function in eliminating neoplastic cells, but also controls the growth and spread of tumor cells of different kinds to other parts of the body. Cancer immunotherapy, is a cancer treatment plan that educates the body’s defensive system to forestall, control, and eliminate tumor cells. The effectiveness of immunotherapy is achieved, to its highest efficacy, by the use of nanoparticles (NPs) for precise and timely delivery of immunotherapies to specific targeted neoplasms, with less or no harm to the healthy cells. Immunotherapies have been affirmed in clinical trials as a cancer regimen for various types of cancers, the side effects resulting from imprecise and non-targeted conveyance is well managed with the use of nanoparticles. Nonetheless, we will concentrate on enhancing cancer immunotherapy approaches by the use of nanoparticles for the productivity of antitumor immunity. Nanoparticles will be presented and utilized as an objective immunotherapy delivery system for high exactness and are thus a promising methodology for cancer treatment.

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BCMA peptide-engineered nanoparticles enhance induction and function of antigen-specific CD8+ cytotoxic T lymphocytes against multiple myeloma: clinical applications

Cited by 41 publications

References 61 publications

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

Recent Progress of Exosomes in Multiple Myeloma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Strategies

Enhancing Cancer Immunotherapy Treatment Goals by Using Nanoparticle Delivery System

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