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.

Occupational-related exposure to diesel exhaust and risk of leukemia: systematic review and meta-analysis of cohort studies.

PURPOSE: Diesel exhaust (DE) is an established lung carcinogen. The association with leukemia is not well established. We conducted a systematic review and meta-analysis of cohort studies to determine the association between occupational DE exposure and risk of leukemia. METHODS: A systematic literature review was performed to identify all cohort studies on occupational exposure to DE and associated risk of leukemia. STROBE guidelines and PECOS criteria were followed. Meta-analyses with fixed effects (and random-effects model in cases of high heterogeneity) were performed to calculate summary relative risks (RR) and 95% confidence intervals (CI), including subgroup analyses by outcome (mortality or incidence), sex, geographic region, industry type, and study quality. Study quality was assessed using the the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort studies. RESULTS: Of the 30 studies retained, 20 (8 from North America, 12 from Europe) reported a total of 33 estimates of the risk of leukemia. Overall, the relative risk (RR) of leukemia was 1.01 (95% CI = 0.97-1.05, I2 = 21.2%, n = 33); corresponding results for leukemia incidence and mortality were RR = 1.02 (95% CI = 0.98-1.06, I2 = 27.9%, n = 19) and RR = 0.91 (95% CI = 0.81-1.02, I2 = 0.0%, n = 15), respectively. The main results were confirmed in analyses by sex and geographic area. A statistically significant association was detected for miners (RR = 1.58, 95% CI = 1.15-2.15, I2 = 77.0%, n = 2) but not for other occupational groups. Publication bias was not detected (p = 0.7). CONCLUSION: Our results did not indicate an association between occupational DE exposure and leukemia, with the possible exception of miners. Residual confounding cannot be excluded.

Applications of PLA in modern medicine.

Polylactic acid (PLA) is a versatile biopolymer. PLA is synthesized with ease from abundant renewable resources and is biodegradable. PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. PLA has demonstrated instrumental importance as a three-dimensionally (3D) printable biopolymer, which has further been bolstered by its role during the Coronavirus Disease of 2019 (Covid-19) global pandemic. As an abundant filament, PLA has created desperately needed personal protective equipment (PPE) and ventilator modifications. As polymer chemistry continues to advance, so too will the applications and continued efficacy of PLA-based modalities.