Abstract:Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.
“…Indeed, it has been shown that the anti-CD38 mAb Daratumumab enhances effectors cell-mediated lysis, degranulation, and ADCC against CD38 + tumor cells [ 84 , 85 , 86 , 87 ] improving the overall response rate in MM patients [ 88 , 89 , 90 , 91 ]. Interestingly, the efficacy of Daratumumab can be enhanced when combined with drugs or other mAbs [ 85 , 90 , 92 ]. Other anti-CD38 mAbs under investigation in hematological malignancies are Isatuximab and MOR-202 [ 93 , 94 , 95 ].…”
Section: Current Advanced Therapy In Hematological Malignanciesmentioning
Natural killer (NK) cells represent one of the first lines of defense against malignant cells. NK cell activation and recognition are regulated by a balance between activating and inhibitory receptors, whose specific ligands can be upregulated on tumor cells surface and tumor microenvironment (TME). Hematological malignancies set up an extensive network of suppressive factors with the purpose to induce NK cell dysfunction and impaired immune-surveillance ability. Over the years, several strategies have been developed to enhance NK cells-mediated anti-tumor killing, while other approaches have arisen to restore the NK cell recognition impaired by tumor cells and other cellular components of the TME. In this review, we summarize and discuss the strategies applied in hematological malignancies to block the immune check-points and trigger NK cells anti-tumor effects through engineered chimeric antigen receptors.
“…Indeed, it has been shown that the anti-CD38 mAb Daratumumab enhances effectors cell-mediated lysis, degranulation, and ADCC against CD38 + tumor cells [ 84 , 85 , 86 , 87 ] improving the overall response rate in MM patients [ 88 , 89 , 90 , 91 ]. Interestingly, the efficacy of Daratumumab can be enhanced when combined with drugs or other mAbs [ 85 , 90 , 92 ]. Other anti-CD38 mAbs under investigation in hematological malignancies are Isatuximab and MOR-202 [ 93 , 94 , 95 ].…”
Section: Current Advanced Therapy In Hematological Malignanciesmentioning
Natural killer (NK) cells represent one of the first lines of defense against malignant cells. NK cell activation and recognition are regulated by a balance between activating and inhibitory receptors, whose specific ligands can be upregulated on tumor cells surface and tumor microenvironment (TME). Hematological malignancies set up an extensive network of suppressive factors with the purpose to induce NK cell dysfunction and impaired immune-surveillance ability. Over the years, several strategies have been developed to enhance NK cells-mediated anti-tumor killing, while other approaches have arisen to restore the NK cell recognition impaired by tumor cells and other cellular components of the TME. In this review, we summarize and discuss the strategies applied in hematological malignancies to block the immune check-points and trigger NK cells anti-tumor effects through engineered chimeric antigen receptors.
“…In addition, other immunotherapies that are showing promise in multiple myeloma clinical trials will hopefully be offered to patients with AL amyloidosis, including chimeric antigen receptor T cells, bispecific T-cell engager antibodies, and antibody–drug conjugates. 68 Fig. 2 Improved survival over time: overall survival (OS) for AL amyloidosis by period of diagnosis.…”
Section: Novel Therapies For Light Chain Amyloidosismentioning
Opportunities and challenges in the field of systemic amyloidosis can be grouped into 4 categories. First, a deeper understanding of the pathogenesis of the disease is required. Second, a greater awareness of the disease, which will lead to an earlier diagnosis, is imperative. Third, end points for interventional trials are required to convey us to our fourth aspirations, which are novel therapies for patients with light chain amyloidosis.
“…Multiple myeloma (MM) remains an incurable haematological malignancy although substantial progress in the treatment has occurred in recent years (1). The introduction of immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide has resulted in significant improvements for the long-term survival and the quality of life of MM patients (2,3). The other drugs, namely proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immune checkpoint inhibitors, and monoclonal antibodies have contributed substantially to improve the prognosis of MM patients (2,4).…”
Section: Introductionmentioning
confidence: 99%
“…The introduction of immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide has resulted in significant improvements for the long-term survival and the quality of life of MM patients (2,3). The other drugs, namely proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immune checkpoint inhibitors, and monoclonal antibodies have contributed substantially to improve the prognosis of MM patients (2,4). Apart from these agents, another way of treatment is autologous stem-cell transplantation (ASCT), which is prescribed for patient populations with limited comorbidities and in good overall condition (5).…”
During recent years considerable progress has been made in the treatment of multiple myeloma. However, despite the current improvements in the prognosis of this malignancy, it always ends with relapse, and therefore new therapy approaches for destroying resistant cancer cells are needed. Presently, there is great hope being placed in the use of immunotherapy against refractory/relapsed multiple myeloma which is unresponsive to any other currently known drugs. The most promising one is CAR-T cell therapy which has already shown tremendous success in treating other malignancies such as acute lymphoblastic leukaemia (ALL) and could potentially be administered to multiple myeloma patients. CAR-T cells equipped with receptors against BCMA (B-cell maturation antigen), which is a surface antigen that is highly expressed on malignant cells, are now of great interest in this field with significant results in clinical trials. Furthermore, CAR-T cells with other receptors and combinations of different strategies are being intensively studied. However, even with CAR-T cell therapy, the majority of patients eventually relapse, which is the greatest limitation of this therapy. Serious adverse events such as cytokine release syndrome or neurotoxicity should also be considered as possible side effects of CAR-T cell therapy. Here, we discuss the results of CAR-T cell therapy in the treatment of multiple myeloma, where we describe its main advantages and disadvantages. Additionally, we also describe the current results that have been obtained on using combinations of CAR-T cell therapies with other drugs for the treatment of multiple myeloma.
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