BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). METHODS: This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III-V) LN patients to receive 3×106 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use. RESULTS: P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3-P13 (excluding P11) received an initial dose of 3×106 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2-6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome. CONCLUSIONS: Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.

A proof of principle investigation of a novel enzyme formulation on dental calculus deposition: a 4-week randomized human clinical trial.

BACKGROUND: The dissolution of dental calculus, safely and at home, is among the more challenging issues facing the over-the-counter healthcare industry. Pontis Biologics, Inc. has developed novel model of calculus development and structure and has formulated a dentifrice (Tartarase™) using digestive enzymes as active ingredients that is shown to dissolve dental calculus in this Proof of Principle clinical trial. METHODS: This investigation was designed to evaluate the safety and efficacy of a novel enzyme formulation to remove existing calculus deposits in 4 weeks, measured using the Volpe-Manhold Index (V-MI) on lingual surfaces of 6 lower anterior teeth. The test formulation was compared to Crest Cavity Protection, as a control dentifrice. A total of 40 randomized test subjects began the study with 20 assigned to the control dentifrice and 20 assigned to the Tartarase groups (ten each, one brushing with Tartarase twice daily and one brushed with Tartarase and wore a dental tray filled with Tartarase for 30 min then brushed again with Tartarase, once daily). RESULTS: The Crest group experienced a 12% increase in calculus, in contrast to the results of both Tartarase groups that experienced a 40% reduction in calculus in 4 weeks of unsupervised at home use of the Tartarase toothpaste formulation. CONCLUSIONS: This proof of principle study demonstrates that a dentifrice, formulated along the lines of the Tartarase material, is capable of combating calculus accumulation using the same oral hygiene habits that are common worldwide. TRIAL REGISTRATION: This trial was registered retrospectively at clinicaltrials.gov and has the Unique Identification Number: NCT06139835, 14/11/2023.

The effect of bupropion sustained-release on cigarette craving after smoking cessation.

BACKGROUND: Most (>50%) smokers who attempt to stop smoking relapse within the first year of abstinence. The effect of continued use of pharmacotherapy for smoking cessation on relapse rates is unknown. Bupropion sustained-release (SR) is the first non-nicotine-based therapy that is effective for achieving abstinence from smoking. OBJECTIVE: This analysis explored the factors involved in relapse to smoking in patients who had successfully stopped smoking using bupropion SR. These patients were participants in a double-blind, placebo-controlled trial of bupropion SR for the prevention of relapse to smoking. METHODS: Participants who had stopped smoking with 7 weeks of open-label bupropion SR were randomly assigned to receive double-blind treatment with either bupropion SR or placebo for 45 weeks. The primary efficacy outcome of the main study was the rate of relapse to smoking. The analyses presented here examine the levels of reported cigarette craving and, in those participants who returned to smoking, the reasons associated with relapse, using patient-completed questionnaires. RESULTS: Craving was cited most frequently as a factor contributing to relapse in those participants receiving placebo (cited by 49.2% of relapsers) but significantly less frequently by participants receiving bupropion SR (cited by 22.4% of relapsers) (P < 0.05). Results from patients' diaries showed no differences between bupropion SR and placebo in terms of "craving in the past 24 hours" but significantly lower scores for "craving right now" for bupropion SR at weeks 11 and 12 (P < 0.05). Results at scheduled visits showed that "craving in the past 24 hours" was significantly less with bupropion SR compared with placebo at weeks 12, 20, and 48, and "craving right now" was significantly less with bupropion SR compared with placebo at weeks 12, 16, 20, 24, 48, and 52 (P < 0.05). CONCLUSIONS: Craving continues to be a significant concern for individuals even after they have successfully stopped smoking. Bupropion SR appears to reduce reported cravings, which may contribute to the overall reduction in the rate of relapse observed with this pharmacotherapy.