Martin Citardi’s Post

Our inaugural issue of The Quill Quartet is here! Four things you might have missed in immunology/rheumatology from the past couple of months. Read more: ▪️Circulating regulatory T cells: https://buff.ly/4f9Qc1i ▪️Digital health in rheumatoid arthritis (RA): https://buff.ly/3W8tgXq ▪️Tyenne approved by the FDA: https://buff.ly/3Wr3Kht ▪️ Long-term safety and efficacy of CAR-T cell treatment in severe and treatment refractory autoimmune disease: https://buff.ly/4fb2LZY More about the CAR-T study: In data presented at EULAR 2024, patients with refractory lupus (SLE n=8), systemic sclerosis (SSc, n=4), and idiopathic inflammatory myositis (IIM=3) were treated with experimental CD19-targeting CAR T cell therapy. At ≥1 year after treatment (median follow-up of 18 months), all 15 patients had stopped immunosuppressive therapy. All patients achieved remission as defined by DORIS remission (SLE), all IIM patients reached ACR/EULAR major response (IIM) and improvement in the EUSTAR activity index (SSc).

What’s the future of bispecific antibodies (BsAbs) in relapsed #MultipleMyeloma? A recent review in Frontiers in Immunology dives into the game-changing role of BsAbs, showing high response rates in heavily pre-treated patients. But what about the best patient population, treatment sequence, and long-term use? Ongoing studies aim to answer these crucial questions. This paper also explores: 🔬 Lower CRS/neurotoxicity vs CAR-T ⚠️ High infection risks 💭 Resistance from chronic BsAb therapy 🧬 Novel T-cell engagers in development Open access article by Rees et al. here: https://ow.ly/XYQW50TKwja #MM #MedEd #MMSM

Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review A #CancerPathogenesisandTherapy study explores #risk factors underlying #hepatic #adverse events in #patients with #cancer who receive #immune #checkpoint #inhibitor #treatment, with the goal to personalize treatment strategies. Read more: https://lnkd.in/g2mCJFes

CD19-directed chimeric antigen receptor (CAR) T-cell therapy, which has transformed the treatment landscape for B-cell malignancies, is now showing great promise in at least three distinct autoantibody-dependent autoimmune diseases. A single infusion of autologous CD19-directed CAR T-cell therapy led to persistent, drug-free remission in 15 patients with life-threatening systemic lupus erythematosus, idiopathic inflammatory myositis, or systemic sclerosis, according to research presented at the American Society of Hematology annual meeting. The responses persisted at 15 months median follow-up, with all patients achieving complete remission,

Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, multiorgan autoimmune condition for which immunotherapeutic treatments have not been established. In NEJM, Oikonomou et al. report the effects of an inhibitor of Janus kinase (JAK) 1 and 2 (JAK1 and JAK2) in a mouse model of APS-1 and a cohort of five patients with the disease. In line with previous reports, the authors showed a key role for interferon-γ signaling in disease pathogenesis. Because interferon-γ signals through JAK1 and JAK2, these findings provide the rationale for testing the effects of a JAK1 and JAK2 inhibitor (ruxolitinib) in APS-1. Treatment of the mouse model of APS-1 and patients with APS-1 resulted in protection from a remarkably diverse array of disease manifestations. These results support the testing of JAK inhibitors as potential first-line immunotherapies for APS-1 in clinical trials.    Read the science behind the study in the editorial “JAK Inhibition Immunotherapy for APS-1” by Maureen Su, M.D.: https://nej.md/4cfs5Mv    Read the study by Vasileios Oikonomou, Ph.D., Michail Lionakis, M.D., Sc.D., et al.: https://nej.md/4bXoKkG    #MedicalResearch 

Our CEO, Lindy Durrant shares her views on the therapeutic cancer vaccines landscape in 2023 and how readouts in 2024 will further inform these advances in antigen targeting, vaccine potency, and patient selection in the latest instalment of @Citeline Commercial’s #ScripAsks. Read the full article here: https://lnkd.in/eNRMWRb8 #immunotherapy #vaccines #immunooncology #biotech #immunology

"Infliximab is an anti-inflammatory medicine for the treatment of rheumatoid arthritis (RA), Crohn’s disease, paediatric CD, ulcerative colitis (UC), paediatric UC, radiographic axial spondyloarthritis (ankylosing spondylitis), psoriatic arthritis (PsA) and psoriasis. Golimumab is also an anti-inflammatory medicine that treats RA, polyarticular juvenile idiopathic arthritis, PsA, radiographic axial spondyloarthritis (ankylosing spondylitis), non-radiographic axial spondyloarthritis and UC." Johnson & Johnson #Medicine #DrugDiscovery #Immunology #InfectiousDiseases #Oncology #Development #Research https://lnkd.in/eqKrZFiT

New from JN Learning: Immune Checkpoint Inhibitor Therapy Before Nephrectomy for Renal Cell Carcinoma https://lnkd.in/g4BjsyqA

No need to wade through lengthy protocols. Fortunately, Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) provides a clear summary of the most recent CHMP plenary results. 🆕 Now available: CHMP-Highlights June 2024. https://lnkd.in/eYJepQeW In the month of June 2024, medicinal products for the following indications have received a positive opinion: ✔️ Urothelial carcinoma ✔️ Emergency treatment of allergic reactions (anaphylaxis) ✔️ Prevention of lower respiratory tract disease (LRTD) caused by Respiratory Syncytial Virus ✔️ Follicular lymphoma and diffuse large B-cell lymphoma ✔️ Paroxysmal nocturnal haemoglobinuria (PNH) ✔️ Positron emission tomography (PET) imaging of the brain ✔️ Pulmonary arterial hypertension Picture: (𝘤) 𝘞𝘦𝘳𝘯𝘦𝘳 𝘏𝘦𝘪𝘣𝘦𝘳 𝘧𝘳𝘰𝘮 𝘱𝘪𝘹𝘢𝘣𝘢𝘺: "𝘉𝘦𝘥, 𝘞𝘰𝘮𝘢𝘯, 𝘞𝘰𝘳𝘬 𝘪𝘮𝘢𝘨𝘦. 𝘍𝘳𝘦𝘦 𝘧𝘰𝘳 𝘶𝘴𝘦."

Allogeneic CAR-T therapy drives autoimmune diseases into remission: Early reports suggest that chimeric antigen receptor (CAR)-T therapy has remarkable potential for treating autoimmune disease. Current approaches rely on autologous CAR-T cells, creating a bottleneck to the broad deployment of this therapy.  A recent publication in Cell reports the first use of allogeneic CAR-T cells in three patients with systemic autoimmune disease. This off-the-shelf cell product (TyU19) was manufactured by isolating T cells from a healthy donor’s peripheral blood mononuclear cells, transducing the T cells with a second-generation CD19 CAR, and then using CRISPR-Cas9 to target TRAC, HLA-A, HLA-B, CIITA, and PD-1 to reduce the risk of immune rejection and graft-versus-host disease (GvHD). These cells were then banked and infused into one patient with immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis. In all three patients, CAR-T cells engrafted and expanded, coinciding with a complete depletion of circulating B cells for at least 2 months. Impressively, all three patients showed significant clinical improvement via respective clinical indexes, molecular markers, and radiographic measures. Remarkably, fibrosis in the lungs and hearts of some patients showed improvement. Although follow-up has only been extended to 6 months, these patients have remained in remission. This scientific discovery holds great potential for future treatment of autoimmune diseases. Original publication: https://lnkd.in/ejPsikBa Further reading: https://lnkd.in/e9DssDqa https://lnkd.in/e2zB33zN https://lnkd.in/eH2aY-XG https://lnkd.in/egSa6gCH https://lnkd.in/eKKdWAWg https://lnkd.in/eFA4mcpN