Immune Checkpoint Inhibitors

More than one third of the patients do not respond to induction therapy (primary nonresponse) and even among initial responders, the response wanes over time. John Berg has been treating Jeffery Monroe with Adalimumab for his IBD. She had begun to exhibit symptoms / or loss of response that may be attributed to subtherapeutic levels of Adalimumab (ADA) and/or the presence of antibodies to

Background: cancer has developed mechanisms to survive and resist drugs including methotrexate, a DHFR inhibitor

In this clinical trial, the T-cell is unlocked by a checkpoint inhibitor, according to the Saving Miss Vanessa article; however, she had to have the correct DNA to qualify for the trial which, happily, she did. She was very fortunate to have the correct DNA as a high percentage do not and they are turned down by this clinical trial. However, it should be noted that some of the possible side-effects include “low-grade rashes or thyroiditis or hypothyroidism…inflame the lungs, colon, or joints or shutdown particular organs” or may even be deadly, as discussed in the article, Saving Miss Vanessa.

Optimal management of NSCLC now requires that tumours be screened for a certain range of predictive and prognostic biomarkers that help to predict sensitivity to targeted therapy and estimate prognosis respectively . For NSCLC, much of the work in the past years has been focussed on mutations of the epidermal growth factor receptor (EGFR) and on the abnormal fusion of the anaplastic lymphoma kinase (ALK) being inhibited successfully with EGFR tyrosine kinase inhibitors (TKI) and crizotinib respectively. Targeted agents are now being rationally designed to inhibit particular mutations leading to a more streamlined clinical trial process. In this review, we will examine the major subtypes of driver mutations that have been identified in NSCLC and relevant targeted therapies available both now, and in the foreseeable future.

CASE STUDY PROGRESS: The client has now received 3 cycles of combination chemotherapy for her breast cancer. Her last treatment with doxorubicin, cyclophosphamide, and 5-fluorouracil was approximately 12 days ago. She came to the emergency room with a 2-day history of fever, chills, and shortness of breath. On arrival, she is disoriented and agitated. Vital signs are 86/43, 119, 28, 39.8° C, SaO2 85% on room air. Laboratory data include WBC 1.2 thou/cmm, Hct 24.9%, Hgb 8.7 g/dl, platelets 125 thou/cmm. Differential WBC count shows 37% granulocytes, 60% lymphocytes, 3% monocytes. Chem 14 is within normal limits, with the exception of BUN 28 mg/dl, creatinine 1.6 mg/dl, and lactic acid 2.4 mg/dl. Chest x-ray demonstrates diffuse infiltrates in the left lower lung.

A key factor in the development of tumors is the ability of cancerous cells to evade recognition from the bodies’ natural defense against cancer, the immune system. Immunotherapies effectively block the pathways that shield cancerous cells from being identified, and thus the promote the bodies own anti-tumor response. However, one challenge to immunotherapy has been its combination with chemotherapy, the mainstay of cancer treatment. While chemotherapy is extremely effective in stopping the rapid division of cancerous cells, its toxic immunosuppressive side-effect make it difficult to combine with

Immunology basically involves understanding the immune system and how it responds to various disease conditions. the immune system consists of a number of components. Traditionally, it is divided into humoral and cellular immune responses. It can also be distinguished into innate and adaptive immunity. The innate immunity can discriminate between normal tissues , self and newly encountered non-self-proteins while the adaptive immunity is the more complex system aimed at the eradication of intracellular pathogens. To do this, antigen derived from such pathogens that are often new to the host organism, need to be recognised by receptor-bearing specialised immune cells which respond to a complex system of stimulatory and costimulatory signals. Better understanding of the human immune system has led to the identification of a number of tumor-associated antigens in the 1980s and the development of various immunotherapeutic approaches. In recent years, identification of the specific antigenic MHC class I epitopes, advancements in genetic engineering, gene delivery, and cell-based therapeutic approaches allowed development of the novel immunotherapeutics.

The established definition of rituximab resistance is the lack of response or the progression within 6 months of treatment to a rituximab-containing regimen.11 Obvious disease progression during rituximab therapy is the most clearly defined form of resistance. Patients who may experience tumor shrinkage have some degree of rituximab sensitivity but are often classified as “resistant” if they fail to achieve either a partial or complete response. Numerous pathways of tumor resistance have been elucidated with conventional chemotherapeutic agents. In some cases, these discoveries have translated into specific interventions aimed at preventing or overcoming tumor resistance.11 Surprisingly, little is known about the determinants of responsiveness

The trial had thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, that were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. The results showed that 26 patients completed the study, with three deaths and one lost to follow-up. Overall, 19 (73.07%) of the patients had improved or stabilized lung disease with the completion of the trial. After the 6-month follow-up period, 12 (54.5%) of the 22 patients showed improved or stabilized lung disease.

Cancer is the uncontrollable division and growth of abnormal cells resulting in formation of an aggressive tumour. In some forms of Breast cancer, the cells proliferate uncontrollably due to over-expression of the protein HER2 (Human Epidermal Growth Factor Receptor 2); a receptor embedded within the membrane of cells, allowing for the transfer of signals outside to inside the cell. Trastuzumab is a monoclonal antibody administered through intravenous infusion, to be taken on its own or in combination with one or more chemotherapy regimens. It reduces risk of the cancer reoccurring or spreading by inhibiting the effects of HER2, and enhancing the body’s immune system.

Intravenous ustekinumab causes a reaction and respite in patients with moderately to severely active Crohn’s disease that is resistant to either tumor necrosis factor(TNF) antagonists or conventional therapy. Among patients who had a reaction to intravenous induction, subcutaneous ustekinumab administered as a dose of 90 mg every 8 weeks or every 12 weeks was more effective than placebo for maintaining remission.

al displayed that following administration of ipilimumab and/or nivolumab in patients with advanced melanoma, many patients had immune/endocrine related adverse events(56). Ryder et al. found that following ipilimumab therapy, the overall incidence of hypophysitis was 8% and hypothyroidism/thyroiditis was 6%(56). Combination therapy of nivolumab and ipilimumab showed associated incidence of 22% for either thyroiditis or hypothyroidism and a 9% incidence of hypophysiitis

Scientists discovered two very important facts about the tumors themselves that explain the malfunction of NK cells. The first one is that an inflammatory

Clinical trials with various combinations of doxorubicin, bleomycin and a platinum-based agent have yielded unsatisfactory results, with response rates of 14 % [5]. Similarly disappointing, the adverse events (AEs) profile of these drugs is dose limiting, with patients experiencing significant neutropenia, nausea/vomiting, diarrhea, anorexia and even congestive heart failure [6]. As the results of conventional treatment modalities have been disappointing and therefore, new therapies are needed. RAI-resistant TC, metastatic MTC and ATC represent one of the most appealing models for biological therapies.

According to Becker (2013), cancer is one of the principal sources of bereavement in our contemporary society. There are roughly 200 different types of cancer. A recent study conducted in 2012 reported that there were 15.1 million new cancer cases, more than 9 million cancer deaths and 33.7 million people living with cancer in 2013 worldwide (p. 23). Cancer cells have the ability to elude immune responses, thereby promoting the development of tumor phenotypes and pathways that bypass the immune cells. The role of the immune system in rebelling