scholarly journals Nivolumab-induced endocrinopathy

2020 ◽  
Vol 66 (6) ◽  
pp. 695-701
Author(s):  
Vitalii Odin ◽  
Valerii Tishko ◽  
Viktoriya Klimenko ◽  
Oksana Shcherbatyuk ◽  
Mikhail Vasilyev ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Case ◽  
Control Points ◽  
Recurrent Colorectal Cancer ◽  
Immune Control ◽  
Normal Tissues ◽  
Immune Mediated ◽  
Organ Systems ◽  
Excessive Activation

Inhibitors of immune control points (ICP) is a new group of drugs used to treat patients with incurable neoplasias, in particular their metastatic forms. However, there is a risk of developing immune-mediated adverse events from a number of organ systems during therapy with these drugs. Immune-mediated adverse events are understood as a side effect due to excessive activation of the immune system with autoimmune damage to normal tissues of various organs and systems, and not the main goal of immunotherapy. In particular, one of these side effects when using ICP is the development of endocrinopathies (thyroiditis, hypophysitis, adrenalitis, type 1 diabetes mellitus). We present a literature review and a clinical case of the development of hypothyroidism, hyponatremia and psychosis in a patient after nivolumab therapy for recurrent colorectal cancer 3 months after immunotherapy.

Autoimmunity associated with immunotherapy of cancer

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 499-509 ◽  
Author(s):  
Sally M. Amos ◽  
Connie P. M. Duong ◽  
Jennifer A. Westwood ◽  
David S. Ritchie ◽  
Richard P. Junghans ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Side Effects ◽  
Cell Transfer ◽  
Serious Adverse Events ◽  
Normal Tissues ◽  
Immune Mediated ◽  
Organ Systems ◽  
Immunotherapy Of Cancer ◽  
Future Potential

Abstract In this age of promise of new therapies for cancer, immunotherapy is emerging as an exciting treatment option for patients. Vaccines and cytokines are being tested extensively in clinical trials, and strategies using monoclonal antibodies and cell transfer are mediating dramatic regression of tumors in patients with certain malignancies. However, although initially advocated as being more specific for cancer and having fewer side effects than conventional therapies, it is becoming increasingly clear that many immunotherapies can lead to immune reactions against normal tissues. Immunotoxicities resulting from treatment can range from relatively minor conditions, such as skin depigmentation, to severe toxicities against crucial organ systems, such as liver, bowel, and lung. Treatment-related toxicity has correlated with better responses in some cases, and it is probable that serious adverse events from immune-mediated reactions will increase in frequency and severity as immunotherapeutic approaches become more effective. This review introduces immunotherapeutic approaches to cancer treatment, provides details of toxicities arising from therapy, and discusses future potential ways to avoid or circumvent these side effects.

scholarly journals Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Ahmad Tarhini
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
T Cell Activation ◽  
Cell Activation ◽  
Treatment Guidelines ◽  
Cell Mediated Immunity ◽  
Low Grade ◽  
Immune Mediated ◽  
Organ Systems ◽  
Treatment Naïve

Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been shown to extend overall survival (OS) in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling with ipilimumab prolongs T-cell activation and restores T-cell proliferation, thus amplifying T-cell-mediated immunity and the patient's capacity to mount an effective antitumor immune response. While this immunostimulation has unprecedented OS benefits in the melanoma setting, it can also result in immune-mediated effects on various organ systems, leading to immune-related adverse events (irAEs). Ipilimumab-associated irAEs are common and typically low grade and manageable, but can also be serious and life threatening. The skin and gastrointestinal tract are most frequently affected, while hepatic, endocrine, and neurologic events are less common. With proper management, most irAEs resolve within a relatively short time, with a predictable resolution pattern. Prompt and appropriate management of these irAEs is essential and treatment guidelines have been developed to assist oncologists and their teams. Implementation of these irAE management algorithms will help ensure that patients are able to benefit from ipilimumab therapy with adequate control of toxicities.

A clinical case of sulodexide usage in infertility of unknown origin

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 72-74
Author(s):  
Igor V. Kurtov ◽  
Alexey M. Osadchuk ◽  
Elena S. Fatenkova ◽  
Alexandra I. Kurtova ◽  
Igor L. Davydkin
Keyword(s):  
Plasminogen Activator ◽  
Clinical Case ◽  
Unknown Origin ◽  
Primary Infertility

The article shows the possible use of sulodexidi in a patient with primary infertility of unknown origin associated with an excess of the plasminogen activator type 1 inhibitor. This method illustrates the possibility of pregnancy when taking sulodexidi at the stage of pregravidar preparation in a woman with hypofibrinolysis.

scholarly journals A Review of Immune-Mediated Adverse Events in Melanoma

2019 ◽  
Vol 7 (2) ◽  
pp. 101-120 ◽  
Author(s):  
Lucy Boyce Kennedy ◽  
April K. S. Salama
Keyword(s):  
Adverse Events ◽  
Immune Mediated

scholarly journals Acute Disseminated Encephalomyelitis (ADEM): A Demyelinating Disease with Specific Morphological Features

2021 ◽  
pp. 106689692199356
Author(s):  
Fleur Cordier ◽  
Lars Velthof ◽  
David Creytens ◽  
Jo Van Dorpe
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Differential Diagnosis ◽  
Clinical Case ◽  
Demyelinating Disease ◽  
Acute Disseminated Encephalomyelitis ◽  
Demyelinating Diseases ◽  
Demyelinating Disorder ◽  
Immune Mediated ◽  
The Central Nervous System

Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory and demyelinating disorder of the central nervous system. Its characteristic perivenular demyelination and inflammation aid in the differential diagnosis with other inflammatory demyelinating diseases. Here, we present a clinical case of ADEM, summarize its histological hallmarks, and discuss pitfalls concerning the most important neuropathological differential diagnoses.

Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders

1998 ◽  
Vol 4 (2) ◽  
pp. 63-69 ◽  
Author(s):  
O A Khan ◽  
H Jiang ◽  
P S Subramaniam ◽  
H M Johnson ◽  
S S Dhib-Jalbut
Keyword(s):  
Therapeutic Option ◽  
High Dose ◽  
Interferon Tau ◽  
Unique Type ◽  
Immune Mediated ◽  
High Concentrations ◽  
Ifn Treatment ◽  
High Doses ◽  
Mulitple Sclerosis

The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review

2017 ◽  
Vol 117 (10) ◽  
pp. 1868-1874 ◽  
Author(s):  
Jo-Ann Sheppard ◽  
Theodore Warkentin ◽  
Andrew Shih
Keyword(s):  
Platelet Count ◽  
Additional Patient ◽  
Heparin Induced Thrombocytopenia ◽  
Prophylactic Dose ◽  
Heparin Administration ◽  
Immune Mediated ◽  
Antibody Levels ◽  
Count Recovery

SummaryOne of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies (“seroreversion”). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

Treatment of solid tumors using bispecific anti-PDL-1/ICOS antibody

2021 ◽  
Author(s):  
Martin Perez-Santos ◽  
Maricruz Anaya-Ruiz ◽  
Gabriela Sanchez-Esgua ◽  
Luis Villafaña-Diaz ◽  
Diana Barron-Villaverde
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Potential Application ◽  
Poor Prognosis ◽  
Bispecific Antibody ◽  
Control Points ◽  
Immune Control ◽  
Ct26 Model

PD-L1 and ICOS are immune control points in cancer and their presence in cancer tends to have a poor prognosis. WO2019122882 patent describes a bispecific antibody that targets PDL-1/ICOS with the potential application of cancer treatment. WO2019122882 patent describes a bispecific antibody with antitumor efficacy in CT26 model through of the depletion of TReg cells and improved ratio of CD8+ T cells: TReg in tumor microenvironment. The anti-PDL-1/ICOS antibody is new; however, only preclinical assays are shown using colon carcinoma model. So far, there are no reports of clinical trials to evaluate the safety, toxicity and efficacy, but it will be of great interest to analyze in the future if this antibody surpasses the action of the combinatorial therapy in cancer.

scholarly journals Immune-related adverse events of immune checkpoint inhibitors: a brief review

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
G. Myers
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Health Care Professionals ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
T Cell Response ◽  
Proactive Management ◽  
Organ Systems

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality.Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy.Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

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