Immune checkpoint inhibitors for cancer treatment

Park, Junsik; Kwon, Minsuk; Shin, Eui‐Cheol

doi:10.1007/s12272-016-0850-5

Cited by 47 publications

(41 citation statements)

References 94 publications

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“…It has two ligands, PD-L1 and PD-L2. PD-L1 is broadly expressed[42]. Several studies have already demonstrated that PD-L1 or PD-1 is highly expressed on tumor cells in gastric cancer patients[43-46].…”

Section: Tils In Gastric Cancermentioning

confidence: 99%

Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology

Kang¹,

Kim²,

Lee³

et al. 2017

WJGO

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Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may cure certain types of cancer. The immune microenvironment of tumors is emerging as the most important means of understanding the relationship between a patient’ immune system and their cancer, informing prognosis, and guiding immunotherapy, such as an antibody blockade of immune checkpoints. For some solid tumors, simple quantitation of lymphocyte infiltration would seem to have prognostic significance, suggesting that lymphocyte infiltration is not passive but may actively promote or inhibit tumor growth. For gastric cancers, several studies have provided strong evidence that immune cells contribute to determining prognosis. However, the exact role of immune cells in gastric cancer remains unclear. Therefore, this review focuses on the clinical significance of immune cells, especially tumor-infiltrating lymphocytes, in gastric cancer.

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Section: Tils In Gastric Cancermentioning

confidence: 99%

Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology

Kang¹,

Kim²,

Lee³

et al. 2017

WJGO

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“…19,20 CTLA-4 acts as a coinhibitory receptor of the CD28-B7 axis, which has a critical role in T-cell response and in cancer escape of tumor surveillance; blocking this pathway prevents induction of tolerance and increases activated T-cell number and repertoire. 18,19,21 Anti-CTLA-4 ipilimumab was the first immuno-oncology therapy to show overall survival (OS) benefit in metastatic melanoma compared with the standard of care, 10,22 and in 2011 ipilimumab initiated the rise of checkpoint inhibitors as cancer therapy ( Figure 1). Anti-PD-1 biologics, such as nivolumab and pembrolizumab, block PD-1 signaling on T cells, and the PD-L1 inhibitors atezolizumab, avelumab, and durvalumab block PD-L1 on tumor cells and/or tumor-infiltrating immune cells; both methods inhibit the interaction between PD-1 and PD-L1 and/or PD-L2 and release the PD-1/PD-L1 immune pathway.…”

mentioning

confidence: 99%

“…2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17] Tumors escape immune surveillance in the host body by various methods, including upregulation of suppressor immune cells, coinhibitory receptor-ligand expression, and production of immunosuppressive cytokines. 18 CTLA-4 and PD-1/PD-L1 have complementary and synergistic roles in regulating T-cell activation ( Figure 2). 19,20 CTLA-4 acts as a coinhibitory receptor of the CD28-B7 axis, which has a critical role in T-cell response and in cancer escape of tumor surveillance; blocking this pathway prevents induction of tolerance and increases activated T-cell number and repertoire.…”

mentioning

confidence: 99%

“…Anti-PD-1 biologics enable T-cell activation and proliferation and may result in subsequent cytokine production, resulting in the restimulation of previously primed T cells for cancer recognition. 18,19,21 In addition, another CTLA-4 checkpoint inhibitor, tremelimumab, is being investigated in phase 3 trials in combination with durvalumab, although it has failed to show superiority as a single agent in randomized studies in melanoma (versus standard of care chemotherapy temozolomide or dacarbazine) and mesothelioma (versus placebo). 23,24…”

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confidence: 99%

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Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors

Sheng

Srivastava

Sanghavi

et al. 2017

The Journal of Clinical Pharma

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Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies. This review outlines the clinical pharmacology characteristics and development challenges for the 6 approved immunomodulatory monoclonal antibodies that target 2 immune checkpoint pathways: ipilimumab (an anti-cytotoxic T-lymphocyte antigen-4 antibody) and, more recently, nivolumab and pembrolizumab (both anti-programmed death-1 antibodies) and atezolizumab, avelumab, and durvalumab (all anti-programmed death ligand-1 antibodies). These agents have revealed much about the clinical pharmacology features of immune checkpoint inhibitors as a class, as well as the pharmacometric approaches used to support their clinical development and regulatory approval. The development experiences with these pioneering immuno-oncology agents are likely to serve as useful guides in the discovery, progression, and approval of future drugs or combination of drugs in this class. This review includes summaries of the pharmacokinetics and exposure-response of the immune checkpoint inhibitors approved to date, as well as an overview of some quantitative systems pharmacology approaches. The ability of immuno-oncology to meet its full potential will depend on overcoming development challenges, including the need for clear strategies to determine optimal dose and scheduling for monotherapy as well as combination approaches. Keywords immunopharmacology, oncology, clinical pharmacology, clinical trials, pharmacology, immunotherapy, checkpoint inhibitorsIt could be said that if there were a book chronicling the history and progression of cancer treatment, we are now moving on from the chapter describing the time of sole reliance on chemotherapy, the chapter outlining the advent of targeted therapy is partially completed, and a new chapter on immuno-oncology is just beginning. The past few years have seen the regulatory approval of several immuno-oncology agents (Figure 1), including 6 immune checkpoint inhibitors: ipilimumab (Yervoy; Bristol-Myers Squibb), pembrolizumab (Keytruda; Merck), nivolumab (Opdivo; Bristol-Myers Squibb), atezolizumab (Tecentriq; Genentech), avelumab (Bavencio; EMD Serono), and durvalumab (Imfinzi; AstraZeneca). 1,2Immunotherapy in oncology is a switch from the cell-killing modality using relatively nonspecific cytotoxic methods (chemotherapy) or therapies that target cancer-specific pathways to methods that employ the patients' immune system to attack cancer. The immuno-oncology approach calls on the understanding of complex signaling processes of effector and regulatory...

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“…The most effective of these immunotherapies to date have been immune checkpoint inhibitors (ICIS), such as ipilimumab, nivolumab and pembrolizumab 22,23 .…”

Section: Principles Of Combining Radiation Therapy With Immunotherapymentioning

confidence: 99%

Combination of radiation therapy and immunotherapy in the treatment of melanoma

Szablewska

Adamczak-Sobczak²

2017

JHOR

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:Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells.In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment.In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.

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Immune checkpoint inhibitors for cancer treatment

Cited by 47 publications

References 94 publications

Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology

Clinical significance of tumor-infiltrating lymphocytes for gastric cancer in the era of immunology

Clinical Pharmacology Considerations for the Development of Immune Checkpoint Inhibitors

Combination of radiation therapy and immunotherapy in the treatment of melanoma

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