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The absence of tumor antigens leads to a low response rate, which represents a major challenge in immune checkpoint blockade (ICB) therapy. Pyroptosis, which releases tumor antigens and damage‐associated molecular patterns (DAMPs) that induce antitumor immunity and boost ICB efficiency, potentially leads to injury when occurring in normal tissues. Therefore, a strategy and highly efficient agent to induce tumor‐specific pyroptosis but reduce pyroptosis in normal tissues is urgently required. Here, a smart tumor microenvironmental reactive oxygen species (ROS)/glutathione (GSH) dual‐responsive nano‐prodrug (denoted as MCPP) with high paclitaxel (PTX) and photosensitizer purpurin 18 (P18) loading is rationally designed. The ROS/GSH dual‐responsive system facilitates the nano‐prodrug response to high ROS/GSH in the tumor microenvironment and achieves optimal drug release in tumors. ROS generated by P18 after laser irradiation achieves controlled release and induces tumor cell pyroptosis with PTX by chemo‐photodynamic therapy. Pyroptotic tumor cells release DAMPs, thus initiating adaptive immunity, boosting ICB efficiency, achieving tumor regression, generating immunological memory, and preventing tumor recurrence. Mechanistically, chemo‐photodynamic therapy and control‐release PTX synergistically induce gasdermin E (GSDME)‐related pyroptosis. It is speculated that inspired chemo‐photodynamic therapy using the presented nano‐prodrug strategy can be a smart strategy to trigger pyroptosis and augment ICB efficiency. [ABSTRACT FROM AUTHOR]

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion: To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO. [ABSTRACT FROM AUTHOR]

Summary: Background: We intended to compare and rank all the immunotherapies including immunosuppressant agents or monoclonal antibodies for myasthenia gravis (MG). Methods: A network meta‐analysis was performed to synthesize the direct evidence and indirect evidence. Quantitative MG score (QMGS) was defined as the primary outcome. The secondary outcomes included the glucocorticoid reduction and hazard ratios (HR) from the counts of adverse events (AEs). Results: We identified 14 studies including 808 MG patients. For the primary outcome, cyclosporine A (CsA) was hierarchically the best with statistical significances of −1.18 (−1.81, −0.59) vs placebo (PLA), −0.98 (−1.72, −0.23) vs mycophenolate mofetil, and −0.77 (−1.57, −0.032) vs tacrolimus (TAC). When the intervention periods were controlled, both eculizumab (ECZ) of −1.50 (−2.81, −0.18) and CsA of −1.23 (−1.81, −0.64) vs PLA reached a statistical significance. Belimumab and ECZ ranked the most tolerable therapies while CsA of 2.41 (0.58, 10.01) ranked the last vs PLA. Conclusion: These findings demonstrated that ECZ represented the most effective and tolerable therapeutic alternative to be recommended for refractory MG. TAC may be a beneficial therapy to treat MG extensively while the efficacy of CsA and cyclophosphamide may be limited by their multiple or severe AEs. [ABSTRACT FROM AUTHOR]