Potential Therapeutic Roles of Exosomes in Multiple Myeloma: A Systematic Review
Multiple myeloma (MM) is the second most prevalent hematological malignancy. In spite of the remarkable progress in understanding the biology and therapy of MM, curing this disease remains difficult, which calls for more effective treatment strategies. As vital communicators between different cells, exosomes have been verified to be crucial to cancer diagnosis, treatment, and prognosis. Exosomes in MM patients show a different expression profile compared with those in healthy individuals. In this review, we summarize potential therapy roles exosomes may play in MM. The specific expression of certain components in exosomes may provide therapeutic targets. Moreover, tumor-derived exosomes and their modified products can be developed into vaccines for anti-tumor immunity. In addition, the natural nano structure of exosomes makes them excellent carriers for drug delivery. Thus, a more rigorous investigation into exosomes will pave the way for novel tumor therapies in MM patients.
(The Mount Sinai Hospital / Mount Sinai School of Medicine) Researchers at the Icahn School of Medicine at Mount Sinai have discovered a way to move precision immunotherapy forward by using genomics to inform immunotherapy for multiple myeloma, a blood cancer, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, in December.
CONCLUSIONS: Our findings demonstrate that somatic mutations in multiple myeloma can be immunogenic and induce neoantigen-specific T-cell activation that is associated with antitumor activity in vitro and clinical response in vivo. Our results provide the foundation for using neoantigen targeting strategies such as peptide vaccines in future trials for patients with multiple myeloma. PMID: 31857430 [PubMed - as supplied by publisher]
Inokuchi Despite therapeutic advances over the past decades, multiple myeloma (MM) remains a largely incurable disease with poor prognosis in high-risk patients, and thus new treatment strategies are needed to achieve treatment breakthroughs. MM represents various forms of impaired immune surveillance characterized by not only disrupted antibody production but also immune dysfunction of T, natural killer cells, and dendritic cells, although immunotherapeutic interventions such as allogeneic stem-cell transplantation and dendritic cell-based tumor vaccines were reported to prolong survival in limited populations of MM p...
Abstract The progression of multiple myeloma (MM), a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in MM have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system have recently shown promise in MM, particularly in the relapsed and/or refractory disease setting. As the efficacy of T-...
In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand-1 (PD-L1) blockade in a murine model of multiple myeloma (MM). MOPC-315 cell lines were injected subcutaneously to establish MM bearing mice.
Cancer immunotherapies have primarily focused on generating tumoricidal CD8 T cells. However, recent data demonstrate a critical role for CD4 T cells in tumor immunity. CD4 T cells against epitopes derived from mutated tumor-associated neo-antigens (neoAg) conferred protection against tumor growth in animal models of neoAg vaccine therapy. In clinical studies, immunity elicited by neoAg vaccines was associated with improved survival, even though the majority of immune responses were CD4 T cells that did not have cytolytic activity.
This article introduces the main concepts and addresses the most relevant clinical modalities of cellular immunotherapies for hematological malignancies: antigen non-specific T cell therapy, genetically modified T cell receptor (TCR) T cell therapy, chimeric antigen receptor (CAR) T cell therapy, and CAR-T cell clinical trials in leukemia, lymphoma, and multiple myeloma. Clinical trials have shown encouraging results, but future studies may need to incorporate novel CAR constructs or targets with enhanced safety and efficacy to ensure long-term benefits. PMID: 31338822 [PubMed - in process]
Multiple myeloma (MM) is an incurable hematological malignancy. Immunodeficiency results in the incapability of immunity to eradicate both tumor cells and pathogens. Immunotherapies along with antibiotics and other anti-infectious agents are applied as substitutes for immunity in MM. Immunotherapies including monoclonal antibodies, immune checkpoints inhibitors, affinity- enhanced T cells, chimeric antigen receptor T cells and dendritic cell vaccines are revolutionizing MM treatment. By suppressing the pro-inflammatory milieu and pathogens, prophylactic and therapeutic antibiotics represent anti-tumor and anti-infection pr...
ConclusionMyeloma has the ability to demonstrate a response to pneumococcal vaccine, independently of preexisting hypogammaglobulinemia and possibly of treatment ‐induced immunodepression. We also observed a drop in the serum response overtime and following autologous transplantation. Further studies in larger sample are needed to understand the benefit of vaccination strategies in these patients.
This study has implications in increasing the efficacy of cancer immunotherapy in MM.