- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, Mesoblast
Review, Journal: Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma. (Pubmed Central) - Nov 13, 2024
We reviewed the current understanding of these multifaceted mechanisms operating in the PDAC microenvironment, influencing the response to chemotherapy, radiotherapy, and immunotherapy regimens. We then describe how the lessons learned from these studies can guide us to discover novel therapeutic regimens to prevent, delay, or revert resistance and achieve durable clinical responses.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, Mesoblast
Journal, Cancer stem, Stroma: Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis. (Pubmed Central) - Sep 14, 2024
In BCSC xenografts, fibroblast IRF6 expression led to an increase in the stromal area and fibroblast density in tumors, in addition to a reduction in necrotic growth. Based on our findings, we propose that fibroblast IRF6 function is an important factor in the development of the stromal microenvironment and in sustaining the BCSC tumor niche.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, Mesoblast
Journal: Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies. (Pubmed Central) - Aug 21, 2024
Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure...Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Journal: Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease. (Pubmed Central) - Mar 15, 2024
Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan...The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks...MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Journal: Tissue-Resident Macrophages Play Divergent Roles in Pancreatitis and Cancer. (Pubmed Central) - Aug 18, 2023
Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis. Tissue-resident macrophage (TRM)-driven stromagenesis differentially affects pancreatitis and pancreatic cancer.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Contego (lifileucel) / Iovance Biotherap
Journal: Bringing function to the forefront of cell therapy: how do we demonstrate potency? (Pubmed Central) - Jul 31, 2023
Both companies completed successful phase III clinical trials but, in both cases, the initial BLA was rejected on the basis that their potency assay for drug product release was inadequate. Fortunately these issues appear to have been overcome in March of this year, with Mesoblast receiving acceptance of their BLA for Remestemcel and Iovance obtaining a rolling BLA approval for Lifileucel.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Journal: Influence of substituting soybean meal with moringa seed cake on feed intake, growth performance, digestibility, blood parameters and economics of fattening crossbred calves. (Pubmed Central) - May 24, 2023
The first group (MSC0%) was fed the CM without any MSC (control), while the second (MSC25%), the third (MSC50%), and the fourth (MSC100%) groups were fed on 25%, 50% and 100% MSC by replacing SBM in CM respectively...Moreover, adding MSC to animals' rations at different levels improved most of blood metabolites compared to control. Conclusion, moringa seed cake can be used as an alternative protein source to soybean meal in fattening calves rations at level up to 50% to improve growth performance and net profit without adverse effects.
- |||||||||| FAPI-74 / Novartis, Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Monitoring FAP CAR T Cell Therapy with PET Imaging (Board No. 589) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1167;
FAP is a cell surface serine protease that is highly expressed by cancer associated fibroblasts in the TME that participate in the generation of the immunosuppressive stromagenic response in solid tumors...In this study, we utilized the 18F-radiolabeled FAP inhibitor (FAPI), [18F]AlF-FAPI-74, to image FAP in two different mouse tumor models...PET imaging is a powerful tool that can have may applications. PET imaging of FAP could be a highly useful approach to stratify patients prior to FAP CAR T therapy, as well as to monitor the pharmacodynamic response for FAP-targeted therapies.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Long-Term Survival in Children Treated with Remestemcel-L for Steroid Refractory Acute Gvhd () - Jan 22, 2023 - Abstract #TCTASTCTCIBMTR2023TCT_ASTCT_CIBMTR_1434;
PET imaging of FAP could be a highly useful approach to stratify patients prior to FAP CAR T therapy, as well as to monitor the pharmacodynamic response for FAP-targeted therapies. There are no recording files available for this presentation
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Preclinical, Journal: FOXL1 + Telocytes in mouse colon orchestrate extracellular matrix biodynamics and wound repair resolution. (Pubmed Central) - Oct 23, 2022
This suggests a role for TC in stromagenesis, but it is hard to identify the specific contribution of TC when analyzing whole tissue profiling studies...However, this ECM-enrichment strategy represents an improvement and interesting avenue to study ECM proteins in the colon compared to total tissue analysis with a background of abundant cellular protein. Thus, the matrisomic approach presented in this study, and its target validation delivered a broader evaluation of the matrix remodeling occurring in the colonic sub-epithelial mesenchyme of the BmpR1a mouse model.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Review, Journal, Checkpoint inhibition: Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer. (Pubmed Central) - Oct 11, 2022
Abnormality of myeloid cells must impact on the entire host, including immune responses, stromagenesis, and cancer cells, leading to refractory cancer...Also, we highlight the possible oncoimmunological components involved in the mechanisms underlying the resistance to the ICI therapy, particularly focusing on myeloid cells, including unique subsets expressing IC molecules. A deeper understanding of the molecular and cellular determinants may facilitate its practical implementation of targeting myeloid villains, and improve the clinical outcomes in the ICI therapy of gastrointestinal cancer.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Journal: Mesenchymal stromal cell therapy for acute respiratory distress syndrome due to coronavirus disease 2019. (Pubmed Central) - Jul 29, 2022
A deeper understanding of the molecular and cellular determinants may facilitate its practical implementation of targeting myeloid villains, and improve the clinical outcomes in the ICI therapy of gastrointestinal cancer. The authors demonstrate in this case series that remestemcel-L infusions to treat moderate to severe CARDS were safe and well tolerated and resulted in improved clinical outcomes.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
THE ROLE OF PRRX1 IN REGULATING KRAS-DRIVEN PANCREATIC ACINAR TO DUCTAL METAPLASIA (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_6279;
Methods : To study the short-term effects of PRRX1 depletion, we generated novel P48cre-ERT;LSLKrasG12D/+;Prrx1fl/fl;Rosa26YFP/YFP (TAM-KCY PRRX1 KO) mice, in which Prrx1 is deleted and YFP is expressed exclusively in pancreatic acinar cells upon tamoxifen induction of Kras activity...Results : Histological analysis demonstrated that PRRX1 loss abrograted ADM formation and stromagenesis as early as Day 5 after pancreatic injury in our TAM-KCY PRRX1 KO mice...Our preliminary data suggest Prrx1 facilitates PDAC progression through PanIN formation. We will continue to investigate the mechanisms driving Prrx1-dependent ADM formation.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
Trial termination, Stroma: MSCs in COVID-19 ARDS (clinicaltrials.gov) - Apr 25, 2022
P3, N=223, Terminated,
Early data suggests improved clinical and endoscopic scores by 2 weeks post MSC delivery. Active, not recruiting --> Terminated; At 3d interim analysis, randomization, but not follow-up, was halted by the DSMB due to low predictive probability of achieving postulated mortality benefit (pre-specified 42.5% relative mortality reduction) were the trial to complete randomization.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma
FOXL1+ TELOCYTES IN MOUSE COLON ORCHESTRATE ECM BIODYNAMICS AND WOUND REPAIR RESOLUTION ([VIRTUAL]) - Mar 25, 2022 - Abstract #CDDW2022CDDW_7;
We have previously shown that BMPR1A signaling deletion in TCFoxL1+ influences the microenvironment via stromagenesis, immune infiltration and colonic dysplasia in mouse model of GI diseases...Conclusions Taken together, these Results suggest that Bmp-signaling deficient TCFoxL1+ significantly contribute to the collagen network biodynamics through increased collagen deposition, fiber alignment reorganization and regulation of the collagen triple-helix assembly. Other matrisome modulations suggest a state of unresolved wound healing due to tissue injury, that could be the etiology of GI pathology and lead to more severe conditions upon various environmental triggers.
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Review, Journal: Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products. (Pubmed Central) - Dec 22, 2021
In this article, the potential of MSC therapy in the treatment of acute GVHD is discussed. A meticulous comparison of studies of remestemcel-L and Temcell, remestemcel-L/Temcell and ruxolitinib, and remestemcel-L/Temcell and thymoglobulin showed that the precise position of remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
Clinical, Journal: Effect of mesenchymal stromal cell infusions on lung function in COPD patients with high CRP levels. (Pubmed Central) - Dec 16, 2021
P2
In an inflammatory environment, defined by elevated circulating CRP, remestemcel-L administration yielded at least transient meaningful pulmonary and functional improvements. These findings warrant further investigation of potential MSC-based therapies in COPD and other inflammatory pulmonary diseases.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
Review, Journal: Cancer-Associated Fibroblasts in Conversation with Tumor Cells in Endometrial Cancers: A Partner in Crime. (Pubmed Central) - Oct 29, 2021
We interrogate the functional characteristics of CAF in the light of its dialogue with tumor cells and other components of TME towards developing a CAF-based strategy for precision therapy to supplement tumor-based therapy. The purpose of the review is to present a new vision and initiate a thought process which recognizes the importance of CAF in a tumor, thereby resulting in a novel approach to the design and management of the disease in endometrial cancers.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
Clinical, Review, Journal: Mesenchymal stromal cells: Getting ready for clinical primetime. (Pubmed Central) - Oct 16, 2021
Earlier this year, the encouraging data for a repeat Phase III trial in pediatric patients with SR-aGVHD was published. This review provides information on the proposed mechanism of action of MSCs, clinical utilization of MSCs with focus on SR-aGVHD and potential modalities that can improve the efficacy of MSCs.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
P3 data, Preclinical, Journal: A Phase 3, Single-arm, Prospective Study of Remestemcel-L, Ex-vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Patients who Failed to Respond to Steroid Treatment for Acute GVHD. (Pubmed Central) - Jun 24, 2021
P3
Remestemcel-L was well-tolerated with no identified infusion-related toxicities or other safety concerns. This study provides robust, prospective evidence of the safety, tolerability and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric SR-aGVHD.
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
Clinical, Review, Journal: Remestemcel-L Therapy for COVID-19-Associated Multisystem Inflammatory Syndrome in Children. (Pubmed Central) - Feb 14, 2021
Across all grades of SR aGVHD, remestemcel-L-rknd was associated with fewer all-grade treatment-emergent adverse events (TEAEs) (27/30) available for comparison, including the majority reaching statistical significance. No abstract available
- |||||||||| Ryoncil (remestemcel-L) / Mallinckrodt, JCR Pharma, Novartis
[VIRTUAL] Effect of Remestemcel-L Treatment in Pediatric Steroid Refractory Acute Graft-Versus-Host Disease: A Biomarker Substudy () - Jan 9, 2021 - Abstract #TCTASTCTCIBMTR2021TCT_ASTCT_CIBMTR_1572;
P3
Remestemcel-L was well tolerated and effective irrespective of graft source, donor type, GVHD severity and prior or concurrent treatment paradigms as defined by the individual protocols. Meaningful clinical outcomes with remestemcel-L- treatment in pediatric SR-aGVHD are associated with changes in soluble and cellular biomarkers consistent with reduced inflammation and risk of mortality and provide evidence of immunomodulation.
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