Abstract 2778: Discovery and preclinical characterization of BAY 1905254 a novel immune checkpoint inhibitor for cancer immunotherapy targeting the immunoglobulin-like domain containing receptor 2 (ILDR2)

Author(s):  
Julia Huetter ◽  
Uwe Gritzan ◽  
Ilona Gutcher ◽  
Sven Golfier ◽  
Wolf-Dietrich Doecke ◽  
...  
Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1672-P
Author(s):  
AMANDA LEITER ◽  
EMILY CARROLL ◽  
DANIELLE C. BROOKS ◽  
JENNIFER BEN SHIMOL ◽  
ELLIOT EISENBERG ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Cristina Valencia-Sanchez ◽  
Anastasia Zekeridou

Paraneoplastic neurological syndromes are more commonly seen with malignancies such as small cell lung cancer, thymoma, gynecological malignancies, and breast cancer as well as seminoma. With the introduction of immune checkpoint inhibitor (ICI) cancer immunotherapy we see an increase of autoimmune neurological complications in patients with malignancies not traditionally associated with paraneoplastic neurological syndromes, such as melanoma and renal cell carcinoma. Immune checkpoint inhibitors enhance antitumor immune responses resulting often in immune-related adverse effects that can affect any organ, including the central and peripheral nervous system, neuromuscular junction and muscle. Neurological complications are rare; neuromuscular complications are more common than central nervous system ones but multifocal neurological presentations are often encountered. The vast majority of neurological complications appear within 3 months of ICI initiation, but have been described even after ICI cessation. Neural autoantibody testing reveals autoantibodies in approximately half of the patients with CNS complications. Early suspicion and diagnosis is critical to avoid worsening and improve outcomes. Therapeutic strategies depend on the severity of the symptoms and initially typically involve discontinuation of ICI and high dose steroids. Further immunosuppression might be necessary. Outcomes are dependent on patient's characteristics and clinical presentations.


2020 ◽  
Vol 18 (3) ◽  
pp. 230-241 ◽  
Author(s):  
John A. Thompson ◽  
Bryan J. Schneider ◽  
Julie Brahmer ◽  
Stephanie Andrews ◽  
Philippe Armand ◽  
...  

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor–related diarrhea/colitis and cardiovascular irAEs.


2020 ◽  
Vol 144 (11) ◽  
pp. 1392-1396
Author(s):  
Irina Sobol ◽  
Carol L. Chen ◽  
Syed S. Mahmood ◽  
Alain C. Borczuk

Context.— Cardiac complications of immune checkpoint inhibitor therapy are rare, but reports of myocarditis are increasing. The findings have been described in case reports as lymphocytic myocarditis, but its histopathology is underreported. Objective.— To review the histology of myocardial biopsy–proven cases of immune checkpoint–associated myocarditis and provide immunohistochemical characterization of the inflammatory infiltrate. Design.— We have encountered 6 patients with biopsy-proven myocarditis in conjunction with therapy using anti–programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) agents with and without cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors and characterized the histopathology and immune cell profile. Results.— The myocarditis was multifocal/diffuse and characterized by a predominant CD163-positive histiocytic infiltrate, with an associated CD8+ and PD-1+ T-lymphocytic infiltrate, some of which were granzyme B positive. Cardiac myocytes showed immunoreactivity for PD-L1 in areas of injury, confirmed using 2 different anti–PD-L1 clones. Four of 6 patients recovered from their cardiac injury. One patient had residual tachycardia-bradycardia syndrome and 1 patient expired. Conclusions.— The diffuse lymphohistiocytic myocarditis associated with this therapy is relatively distinctive, and this diagnosis is strongly suggested based on the histopathologic findings in the correct clinical setting.


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