Polymyalgia rheumatica and giant cell arteritis induced by immune checkpoint inhibitors: A systematic literature review highlighting differences from the idiopathic forms

Review

作者: Cutolo, Maurizio ; Hysa, Elvis ; Gotelli, Emanuele ; Tanda, Enrica Teresa ; Genova, Carlo ; Sulli, Alberto ; Casabella, Andrea ; Campitiello, Rosanna ; Cimmino, Marco Amedeo ; Schenone, Carlotta ; Paolino, Sabrina ; Smith, Vanessa

INTRODUCTIONAn altered immune tolerance disturbed by immune checkpoint inhibitors (ICIs) may contribute to new-onset polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). This systematic literature review (SLR) examines the characteristics of PMR and GCA-like syndromes following anticancer treatment with ICIs, summarizing their demographic, clinical and treatment-related features to provide insights whether they differ from the idiopathic forms.METHODSThe SLR was conducted in Medline and EMBASE databases from inception to July 2024, and in the EULAR/ACR abstract database (2021-2023). ICI-induced PMR and GCA syndromes were compared to the primary forms of the diseases using data from studies that included both groups as comparators. For manuscripts lacking direct comparisons, we summarized the main findings and discussed the differences using systematic reviews or large observational studies on the primary forms.RESULTSFrom 1237 screened abstracts, 46 met the inclusion criteria, involving 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had an estimated pooled prevalence of 0.1% [95% CI: 0.07%, 0.14%] among ICI recipients and 15.9% [95% CI: 12.6%, 19.9%] among patients experiencing rheumatic immune-related adverse events. Patients with ICI-PMR had a male-to-female ratio of 1.7:1 and a mean age of 71 ± 4 years. Most cases were associated with PD1/PDL1 blockers (87%). Clinical features included inflammatory pain in the girdles (100%), though pelvic girdle involvement was under-reported in some cases (3/28 studies). Peripheral arthritis was present in 35% of patients. Laboratory tests showed normal or slightly elevated inflammatory markers in 26% of cases. Glucocorticoids (GCs) led to symptom improvement in 84% of cases although 20% required immunosuppressive treatment and 14% experienced relapses. ICI-GCA had a prevalence of 0.06% among ICI recipients, with equal gender distribution and a mean age of 71 ± 5 years. Most patients received anti-PD1/PDL1 blockers (57%). Clinical manifestations included cephalic symptoms (75%), permanent visual loss (23%) and symptoms related to large-vessel involvement (54%). High-dose GCs were effective, with 96% achieving remission, though 17% experienced relapses.CONCLUSIONSICI-induced PMR and GCA may have distinct clinical profiles compared to idiopathic forms, with potentially milder symptoms and better treatment responses. Further studies are needed to confirm these findings and better understand the long-term outcomes and pathophysiology of these conditions.

2024-05-01·Biotechnology Progress

Evaluation of PDL1 positive cancer cell‐specific binding activity of recombinant anti‐PDL1 scFv

Article

作者: Kim, Sun‐Hee ; Jeong, Hee‐Jin ; Park, Hae‐Min

AbstractProgrammed cell death‐ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single‐chain fragment of variable domain (scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof‐of‐concept data for the effect of scFv using PDL1‐expressing cells was lacking. In this study, we conducted two kinds of cell‐based immunoassays, western blotting and enzyme‐linked immunosorbent assay, using anti‐PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell‐based immunoassays to detect PDL1.

Small

Ultrasound Guided Local Delivery of Bioorthogonal PDL1 Degrader for Enhanced Immunotherapy

Article

作者: Yang, Guodong ; Yuan, Lijun ; Wei, Mengying ; Liu, Zhaoyou ; Mou, Ke ; Gong, Li ; Ma, Jiao ; Ji, Panpan ; Zhou, Tian ; Sun, Wenqi ; Wang, Lantian ; Zhang, Bin ; Liang, Yuan

AbstractImmunotherapy involving PDL1 degradation holds great potential in anti‐tumor treatment. Optimal design of PDL1 degraders and subsequent efficient delivery into tumors are essential for expected efficacy, especially when abnormal tumor vasculature is considered. Herein, a nanodroplet‐based novel drug delivery platform termed as NDsmTx (nanodroplet‐based therapeutics) for ultrasound targeted delivery of PDL1 degrader is designed. Briefly, the shell of the NDsmTx is armed with RGD and mPD1 (a bioorthogonal PD1 mutant produced by genetic codon expansion technology can covalently bind PDL1), and the core is composed of perfluorohexane (PFH, C6F14). The RGD on the NDsmTx recognizes αvβ3 expressed by tumor vasculature, making NDsmTx accumulated in tumor practical and visible by low‐frequency ultrasound (LFUS). In turn, inertial cavitation induced by LFUS facilitates mPD1 on the nanodroplet debris penetrating the tumor, where mPD1 covalently binds PDL1 and initiates a lysosomal degradation process. Through both in vitro and in vivo study, the superior performance of NDsmTx in degrading PDL1 and boosting anti‐tumor immunity is confirmed. In conclusion, NDsmTx emerge as an alternative to existing PDL1 blockers in tumor immunotherapy.

100 项与 PDL1 modulators(University of Vienna) 相关的药物交易

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