CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients

Abstract

The chimera antigen receptor (CAR) T cell therapy is a novel and potential targeted therapy and has achieved satisfactory efficacy in patients with relapsed or refractory multiple myeloma (MM) in recent years. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics. To explore the potential biomarkers in plasma for evaluating CRS and clinical efficacy, we performed metabolomic and lipidomic profiling of plasma samples from 17 relapsed or refractory MM patients received CAR-T therapy. Our study showed that glycerophosphocholine (GPC), an intermediate of platelet-activating factor (PAF)-like molecule, was significantly decreased when the participants underwent CRS, and the remarkable elevation of lysophosphatidylcholines (lysoPCs), which were catalyzed by lysoPC acyltransferase (LPCAT) was a distinct metabolism signature of relapsed or refractory MM patients with prognostic value post-CAR-T therapy. Both GPC and lysoPC are involved in platelet-activating factor (PAF) remodeling pathway. Besides, these findings were validated by LPCAT1 expression, a key factor in the PAF pathway, associated with poor outcome in three MM GEP datasets of MM. In conclusion, CAR-T therapy alters PAF synthesis in MM patients, and targeting PAF remodeling may be a promising strategy to enhance MM CAR-T therapy.

G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/β-catenin pathway

“…The serum samples from all subjects were collected and stored in a digital-alarm-controlled freezer at − 80 °C until required for analysis. Sample preparation for the untargeted metabolomics analysis was performed as described in a previous study [ 26 ]. The Thermo Scientific ™ Vanquish ™ Horizon UHPLC system coupled to a Thermo Scientific ™ Q Exactive hybrid quadrupole-Orbitrap mass spectrometer (Thermo Fisher Scientific, Inc., Waltham, MA, USA) operated in full scan mode was used for the untargeted analysis of serum samples.…”

CD229 interacts with RASAL3 to activate RAS/ERK pathway in multiple myeloma proliferation

“…Our group is dedicated to the discovery of novel therapeutic targets in MM. As previously reported, we found that targeting platelet-activating factor (PAF) remodeling might be a promising strategy to enhance MM CAR-T therapy [ 30 ]. In present study, our findings further disclose that CD229 regulates MM cell proliferation through the RAS/ERK pathway and CD229 can be considered as a promising target in diagnosis and treatment of MM.…”

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine

“…The auto-sampler was conditioned at 4°C. Untargeted metabolomics were detected as described in a previous study ( 6 ).…”

“…In 2003, Velcade (bortezomib for injection) was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MM as the first proteasome inhibitor (5). The latest clinical MM therapy is a new immunomodulatory therapy using chimeric antigen receptor T cells, bispecific T cell conjugates, and immune checkpoint inhibitors (6). Although the therapeutic armamentarium for MM has continued to evolve (7)(8)(9)(10)(11)(12)(13)(14), MM still possesses the characteristics of high relapse and incurability.…”