Delivery of Immune Checkpoint Inhibitors Using Nanoparticles
Hala Gali-Muhtasib, Racha Chouaib in Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Currently, immunotherapy is one of the most promising cancer treatments [2] and the development of new immunotherapies has become a necessity [3, 4]. In recent years, immunotherapy has become widespread and has been used to treat both hematological and solid cancers [2]. Immunotherapy is a biological therapy that involves activation of the immune system to target and kill cancer cells through different approaches. Promising immunotherapy approaches include adoptive cell transfer, therapeutic monoclonal antibodies (mAbs), treatment vaccines, cytokine treatment using interferons and interleukins, Bacillus Calmette Guérin (BCG), which is a weakened bacterium used in the treatment of bladder cancer, and immune checkpoint inhibitors. Chimeric antigen receptor therapy also known as CAR T-cell therapy has stood out as a clinically effective type of adoptive cell transfer therapy. Immune checkpoint inhibitors, in particular, have shown potential in the treatment of several cancers and have been FDA approved for the treatment of melanoma (recurrent and/or metastatic), non-small cell lung cancers (NSCLCs), genitourinary cancers (GUCs), head and neck cancers (HNCs), renal cell carcinomas, urothelial carcinomas, non-Hodgkin lymphomas and other cancers [5].
Effects of treatment on the thorax
Anju Sahdev, Sarah J. Vinnicombe in Husband & Reznek's Imaging in Oncology, 2020
Immunotherapy is increasingly used in the management of cancer. A wide array of cancer immunotherapeutic agents are currently available including cytokines, cancer vaccines, adoptive cellular therapy, and, more recently, the immune checkpoint inhibitors (94–98). Immune checkpoint inhibitors are designed to overcome evasion of immune responses by cancer cells and include drugs which inhibit PD-1 (pembrolizumab, nivolumab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab). Currently, these FDA-approved drugs are used in a variety of solid and haemotological cancers. Although these agents are promising from a therapeutic standpoint, they are associated with significant immune-related adverse events, which can affect any organ. Pneumonitis is one such rare, but potentially fatal, complication and is seen in 2.7%–6.6% of patients (99). The clinical course in this condition is highly variable. Patients may experience mild symptoms, which readily respond to corticosteroids; at the other extreme, patients may be afflicted with fulminant pneumonitis, necessitating critical care. The CT manifestations are variable, including acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern, non-specific interstitial pneumonia (NSIP) pattern, cryptogenic organizing pneumonia (COP) pattern, and hypersensitivity pneumonitis pattern (Figure 38.15) (Table 38.1) (100–102).
Application of Viral Nanomaterials in Medicine
Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji in Viral and Antiviral Nanomaterials, 2022
Current cancer therapies, such as chemotherapy and radiotherapy, have many side effects and toxicity; however, immunotherapy is an effective clinical treatment for various cancers. Chemotherapeutic drugs inhibit the uncontrollable cell division but also affect the normal cells surrounding the cancerous cells. Therefore, the merger nanotechnology and immunotherapy is significant in treating cancers by allowing the delivery of drugs to the targeted sites using nanoparticles; in turn, it enhances the immune responses to fight against tumours (Pérez-Herrero and Fernández-Medarde 2015). Phagocytes, which play a critical role in both immunosupression and immunostimulation, uptake engineered NPs with immunostimulatory agents and thus induce antitumour immune responses (Sheen et al. 2014).
Pembrolizumab related Guillain barre syndrome, a rare presentation in a patient with a history of lupus and bladder cancer
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Vikram Sangani, Mytri Pokal, Mamtha Balla, Ganesh Prasad Merugu, Sreedhar Adapa, Srikanth Naramala, Venu Madhav Konala
Pembrolizumab is an anti-PD-1 IgG monoclonal antibody that was first approved by Food and Drug Administration (FDA) in September 2014 in advanced melanoma who progressed following treatment with ipilimumab and a BRAF inhibitor in patients with BRAF mutation [1]. Since then it has been approved as the first line, second line and third line management either alone or in combination with chemotherapeutic agents for multiple cancers. Pembrolizumab blocks the PD1 receptor, also known as an immune checkpoint on lymphocytes, and allows the immune system to destroy cancer cells. Due to its action, it is also called the Immune checkpoint inhibitor (ICI) [2]. Immunotherapy is being increasingly used in clinical practice and is better tolerated than chemotherapy with common side effects of pruritus, fatigue, rash, nausea, diarrhea, decreased appetite, and asthenia apart from autoimmune side effects. We need to monitor for autoimmune side effects, as the activated immune system carefully can attack any organ, with thyroid being the most affected organ [2–4]. Sporadic cases of Guillain-Barré syndrome (GBS) have been mentioned with the use of ICI [5]. We are presenting a rare case of GBS, which developed secondary to the use of pembrolizumab used to treat bladder cancer in our patient.
Programmed cell death protein 1 (PD-1)-inhibition in hepatocellular carcinoma (HCC): a single center experience
Published in Scandinavian Journal of Gastroenterology, 2020
Robert Mahn, Annabelle Vogt, Patrick Kupczyk, Farsaneh Sadeghlar, Katrin van Beekum, Robert Hüneburg, Carsten Meyer, Marieta Toma, Hojjat Ahmadzadehfar, Markus Essler, Hanno Matthaei, Philipp Lingohr, Jörg C. Kalff, Christian P. Strassburg, Maria A. Gonzalez-Carmona
Distribution of adverse events is shown in Table 2. Despite the advanced stage of disease, immunotherapy was well tolerated by all patients. As expected, immune-related colitis, hepatitis and rash were the most frequently observed adverse events. In four patients (28.5%), we registered grade 3 irAE. 2 patients had to interrupt the immunotherapy for a period of time due to side effects and two patients with grade 3 irAE (severe colitis and thrombopenia) had to discontinue the immunotherapy. Immune-related AE were treated according to the recommend guidelines with corticosteroids for grades 3 and 4. Frequently, patients complained of fatigue under immunotherapy, which was more related to the underlying liver cirrhosis than to the immunotherapy. However, immune related hypophysitis was found as the cause of fatigue in one patient. Interestingly, all patients showing irAE (grade 3) seem to benefit from the immunotherapy more likely despite immunotherapy breaks in some cases and despite the administration of steroids.
MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression
Published in OncoImmunology, 2022
Jinti Lin, Ankai Xu, Jiakang Jin, Man Zhang, Jianan Lou, Chao Qian, Jian Zhu, Yitian Wang, Zhengming Yang, Xiumao Li, Wei Yu, Bing Liu, Huimin Tao
In recent years, immunotherapy has been found to be effective in various cancers.8–10 For example, chimeric antigen receptor-modified T (CAR-T) cell immunotherapy has been used for treatment of malignant tumors of the lymphoid hematopoietic system;8,11 and immune checkpoint therapy has become a famous strategy in a variety of malignant tumors (melanoma, non-small- cell lung cancer, breast cancer, colorectal cancer, etc.).10,12–16 Considering multiple chromosomal abnormalities and high mutation burden in osteosarcoma, immunotherapy might be a promising option.5,17 However, current clinical trials of immunotherapy for osteosarcoma have not received satisfactory effects.5,18–20 Thus, a new immunotherapy strategy needs to be explored.
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