scholarly journals The importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer

2022 ◽  
Vol 146 ◽  
pp. 112516
Author(s):  
Hajar Alemohammad ◽  
Basira Najafzadeh ◽  
Zahra Asadzadeh ◽  
Amir Baghbanzadeh ◽  
Farid Ghorbaninezhad ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
Immune Monitoring ◽  
Immune Checkpoints

An anti–glypican 3/CD3 bispecific T cell–redirecting antibody for treatment of solid tumors

2017 ◽  
Vol 9 (410) ◽  
pp. eaal4291 ◽  
Author(s):  
Takahiro Ishiguro ◽  
Yuji Sano ◽  
Shun-ichiro Komatsu ◽  
Mika Kamata-Sakurai ◽  
Akihisa Kaneko ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Immune Monitoring ◽  
Immune Checkpoints ◽  
Gpc3 Expression

Cancer care is being revolutionized by immunotherapies such as immune checkpoint inhibitors, engineered T cell transfer, and cell vaccines. The bispecific T cell–redirecting antibody (TRAB) is one such promising immunotherapy, which can redirect T cells to tumor cells by engaging CD3 on a T cell and an antigen on a tumor cell. Because T cells can be redirected to tumor cells regardless of the specificity of T cell receptors, TRAB is considered efficacious for less immunogenic tumors lacking enough neoantigens. Its clinical efficacy has been exemplified by blinatumomab, a bispecific T cell engager targeting CD19 and CD3, which has shown marked clinical responses against hematological malignancies. However, the success of TRAB in solid tumors has been hampered by the lack of a target molecule with sufficient tumor selectivity to avoid “on-target off-tumor” toxicity. Glypican 3 (GPC3) is a highly tumor-specific antigen that is expressed during fetal development but is strictly suppressed in normal adult tissues. We developed ERY974, a whole humanized immunoglobulin G–structured TRAB harboring a common light chain, which bispecifically binds to GPC3 and CD3. Using a mouse model with reconstituted human immune cells, we revealed that ERY974 is highly effective in killing various types of tumors that have GPC3 expression comparable to that in clinical tumors. ERY974 also induced a robust antitumor efficacy even against tumors with nonimmunogenic features, which are difficult to treat by inhibiting immune checkpoints such as PD-1 (programmed cell death protein–1) and CTLA-4 (cytotoxic T lymphocyte–associated protein–4). Immune monitoring revealed that ERY974 converted the poorly inflamed tumor microenvironment to a highly inflamed microenvironment. Toxicology studies in cynomolgus monkeys showed transient cytokine elevation, but this was manageable and reversible. No organ toxicity was evident. These data provide a rationale for clinical testing of ERY974 for the treatment of patients with GPC3-positive solid tumors.

scholarly journals Role of Cardiac Imaging in the Diagnosis of Immune Checkpoints Inhibitors Related Myocarditis

2021 ◽  
Vol 11 ◽  
Author(s):  
Stéphane Ederhy ◽  
Joe-Elie Salem ◽  
Laurent Dercle ◽  
Abrar Saqif Hasan ◽  
Marion Chauvet-Droit ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
Checkpoint Inhibitors ◽  
Clinical Syndrome ◽  
Immune Checkpoints ◽  
Patients With Cancer ◽  
High Fatality Rate ◽  
Clinical Scenarios ◽  
Low Incidence ◽  
Electrocardiogram Ecg

Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (<1%) but with a high fatality rate (30−50%). ICI-related myocarditis has been attributed to an immune infiltration, comprising of T-cells that are positive for CD3+, CD4+, CD8+, and macrophages that are positive for CD68. The diagnosis remains challenging and is made based on clinical syndrome, an electrocardiogram (ECG), biomarker data, and imaging criteria. In most clinical scenarios, endomyocardial biopsy plays a pivotal role in diagnosis, while cardiac magnetic resonance imaging (cMRI) has limitations that should be acknowledged. In this review, we discuss the role of medical imaging in optimizing the management of ICI related myocarditis, including diagnosis, prognostication, and treatment decisions.

A Possible Paradigm Shift in Thinking About Thinking

1985 ◽  
Vol 30 (1) ◽  
pp. 17-17
Author(s):  
Marion Perlmutter
Keyword(s):  
Paradigm Shift

The Postindustrial Paradigm Shift: From Roles to Relationships

1994 ◽  
Vol 39 (2) ◽  
pp. 197-198
Author(s):  
Raymond T. Garza
Keyword(s):  
Paradigm Shift

Extreme Teams: Is a Paradigm Shift Required?

2011 ◽  
Author(s):  
Wendy L. Bedwell ◽  
Aaron S. Dietz ◽  
Kathryn E. Keeton ◽  
Daniel Tani ◽  
Gerald Goodwin ◽  
...  
Keyword(s):  
Paradigm Shift

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

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