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Patients of RRMM have a poor prognosis, and their treatment options are limited. In RRMM, the latest available results from clinical trials on CAR-T cell therapy have demonstrated safety and manageable toxicity. In RRMM, the CAR-T cells were mostly focused on well-known cellular targets, such as B-cell maturation antigen. With an overall response rate and a median progression-free survival in RRMM, autologous CAR-T cell therapy against BCMA has the highest success. The key problems in the routine use of CAR-T cells are high treatment prices and uncertainty about long-term results. We summarize the most recent review of CAR-T cell therapy in RRMM in 2021, including various targets for CAR-T cells' safety, stability, and potential flaws. Future prospective clinical trials are required to establish the correct role of CAR-T cells in MM therapy.
Source link: https://europepmc.org/article/MED/35900317
Background: On multiple myeloma blisters, chimeric antigen receptor T cell therapy affecting B cell maturation antigen on multiple myeloma cells is fast but not long-lasting responses. We found rapid BCMA downmodulation on target cells with all three tested binding moieties on CAR T cell contact at eloma cell contact. CAR T cells were injected with BCMA on their cell surface by trogocytosis, and BCMA on MM cells was rapidly internalized. Since trogocytosis can result in CAR T cell exhaustion, and the presence of CAR T cells does not prevent patients from relapse, we investigated whether non-functional CAR T cells play a role in tumor formation. Although CAR T cell and cell interactions stimulated the BCMA pathway, we did not find enhanced tumor formation in vitro or in vivo, we did not find increased tumor formation in vitro or in vivo. Our research illuminates the causes of CAR T cell failure in MM and informs the development of more targeted therapy strategies.
Source link: https://europepmc.org/article/PPR/PPR523158
Multiple myeloma patients can be treated by autologous cell immunotherapy using B cell maturation antigen receptor -targeted chimeric antigen receptor - T cells, which is an effective novel therapy. This therapy has only been used for relapsed and refractory patients, at which time the endogenous T cells used to produce the CAR-T cells are influenced by the immunosuppressive properties of new therapies' advanced MM and/or side effects of previous therapies. T cells from leukocytoapheresis cells that are routinely collected to obtain hematopoietic progenitor cells for autologous stem cell transplantation early in MM's disease. Anti-BCMA CAR-T cells can only be identified by T cell phenotypes if G-CSF treatment negatively influences T cell phenotype and can determine if recent exposure of T cells to G-CSF is deleterious for anti-BCMA CAR-T cells. ASCT apheresis cells, according to the study, are a suitable source of T cells for anti-BCMA CAR-T cell manufacture.
Source link: https://europepmc.org/article/MED/35859694
Chimeric antigen receptor T-cell therapy has had promising results in hematologic malignancies. Here's the first review of clinical data from 18 patients with multiple myeloma who underwent immunotherapy with BCMA-CAR-T cells. The results showed that the basal serum level of IP-10 was positively related to patient outcomes one year after CAR-T-cell therapy, and that a higher basal serum level of IP-10 was positively linked to progression-free survival. The results showed that IP-10 could effectively boost CD8+ CAR-T cells' chemotaxis. In addition, CAR-T cells cultured in IP-10-supplemented medium had a higher growth rate and a more effective way to kill tumour cells at a higher rate: target ratio. Our results show that IP-10 can improve CAR-T cells' function, which has important implications for CAR-T-cell immunotherapy for haematologic malignancies.
Source link: https://europepmc.org/article/PPR/PPR506745
Multiple myeloma is the second most common hematological disorder that also doesn't have effective medical therapies. MM with central nervous system invasion in particular is extremely unusual. Although B-cell maturation antigen receptor-T cell therapy has demonstrated high success for the treatment of relapsed/refractory MM, no studies have reported whether BCMA CAR-T can reduce MM with CNS invasion. Case presentation In this report, we present a special case of a 63-year-old male patient who developed CNS inflammation and demonstrated rapid extravascular disease progression into multiple organs. Conclusion This case report demonstrated that BCMA CAR-T could safely eliminate CNS-involved MM with low adverse events, implying that CAR-T cell therapy may be a viable therapeutic option for this type of refractory disease.
Source link: https://europepmc.org/article/MED/35651792
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