Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma

Ivashko, Igor N.; Kolesar, Jill M.

doi:10.2146/ajhp140768

Cited by 74 publications

(42 citation statements)

References 32 publications

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“…In metastatic melanoma, ipilimumab, pembrolizumab and nivolumab have shown significant survival benefits when compared to traditional chemotherapy, with five year survival rates up to 25 to 31% 7,8 . In NSCLC, those treated with nivolumab had a 51% survival at 12 months, compared to 39% with docetaxel 9 .…”

Section: Introductionmentioning

confidence: 99%

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Cappelli

Shah²,

Bingham³

2017

Rheumatic Disease Clinics of North America

105

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Summary Immune checkpoint inhibitors (ICIs) are being increasingly studied and used as therapy for a growing number of malignancies. ICIs work by blocking inhibitory pathways of T-cell activation, leading to an immune response directed against tumors. Such nonspecific immunologic activation can lead to immune-related adverse events (IRAE). Some IRAE including inflammatory arthritis, sicca syndrome, myositis and vasculitis are of special interest to rheumatologists. As use of ICIs increases, recognition of these IRAEs and developing treatment strategies will become important. In this review, the current literature on rheumatic and musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and treatment considerations are highlighted.

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Section: Introductionmentioning

confidence: 99%

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Cappelli

Shah²,

Bingham³

2017

Rheumatic Disease Clinics of North America

105

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“…Upon PD-1 interaction, a kinase signaling pathway that normally results in T-cell activation is inhibited; thus, immunotherapy strategies that interfere with the PD-1 checkpoint have shown enhanced anticancer activity in the clinic. There are currently two FDA-approved antibodies targeting PD-1: pembrolizumab (Keytruda®, Merck & Company, Inc.) and nivolumab (Opdivo®, Bristol-Myers Squibb) (10). While these two antibodies have the same biological target, their binding affinities and production source are different.…”

Section: Programmed Cell Death 1 (Pd-1)mentioning

confidence: 99%

“…The source of production also differs, as pembrolizumab is a humanized murine antibody while nivolumab is a fully human antibody. Despite these differences, the objective response rates in advanced melanoma were similar between pembrolizumab (26-38%) and nivolumab (31-40%) (10), suggesting that the therapeutic dosages may be saturating the receptor in therapy. PD-1 targeted treatments have shown fewer adverse effects than those employing the CTLA-4 pathway; however, significant immune-mediated responses were still reported during clinical trials (11,12).…”

Section: Programmed Cell Death 1 (Pd-1)mentioning

confidence: 99%

Molecular Imaging of Immunotherapy Targets in Cancer

et al. 2016

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Immunotherapy has emerged as a promising alternative in the arsenal against cancer by harnessing the power of the immune system to specifically target malignant tissues. As the field of immunotherapy continues to expand, researchers will require newer methods for studying the interactions between the immune system, tumor cells, and immunotherapy agents. Recently, several noninvasive imaging strategies have been employed to map the biodistribution of immune checkpoint molecules, monitor the efficacy and potential toxicities of the treatments, and identify patients who are likely to benefit from immunotherapies. In this review, we outline the current applications of noninvasive techniques for the preclinical imaging of immunotherapy targets, and suggest future pathways for molecular imaging to contribute to this developing field.

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“…Following chronic T-cell activation, the inhibitory receptor PD-1 is induced on T cells and the expression of one of its ligands PD-L1 on macrophages and the tumour cells can offer protection from immune destruction [14]. As a result, targeting either PD-1 or PD-L1 offers an opportunity to disable a major mechanism of tumourmediated immune evasion.…”

Section: Immune Checkpoint Inhibition -Basic Aspectsmentioning

confidence: 99%

“…Pembrolizumab, a humanised antibody, was the second anti-PD1 antibody to enter large-scale clinical trials [14]. Pembrolizumab demonstrated remarkable activity in patients with advanced-stage melanoma, both in patients previously treated with ipilimumab and in those who were not treated with ipilimumab [16].…”

Section: Immune Checkpoint Inhibition -Basic Aspectsmentioning

confidence: 99%

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Pistamaltzian

Perez

Baxevanis

2016

Forum of Clinical Oncology

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There is now increasing evidence to suggest that adaptive immunity plays a major role in regulating the growth of tumour cells. T cells play a major role in coordinating the immune response against tumourspecific antigens during tumour progression. While T cell activation depends on the initial tumour antigen-specific signal provided to the T cell receptors via the antigenloaded major histocompatibility complex (MHC) complex on dendritic cells (DCs), additional signals provided by costimulatory molecules fine-tune this response, determining its strength, nature and duration. To this end, the discovery of receptors regulating T cell activation against the autologous tumour was of paramount importance for understanding how cancer progresses under immunosurveillance. The CD28 co-receptor acts as a strong positive costimulatory receptor, and CTL antigen-4 (CTLA-4) as a potent co-inhibitory receptor. The programmed death 1 (PD-1) receptor: PD-Ligand (PD-L) pathway is another major receptor-ligand network that functions primarily to provide a co-inhibitory signal. PD1: PD-L interactions maintain peripheral tolerance and are exploited by tumours to evade immune eradication by memory T cells specifically recognizing tumour peptides [1]. As such, this pathway has emerged as a potential therapeutic target for enhancing the immune response. A second important discovery, which also sheds light to our understanding of tumour evolution, is presented by the "immunoediting" theory. According to this theory, the immune system "edits" the tumour immunogenicity, resulting in the promotion or suppression of tumour growth, a phenomenon [2]. As a result of its capacity to shape tumour immunogenicity, an additional role for the immune system has emerged, namely that of prognostic indicator. Studies by Galon et al. [3], initiated almost a decade ago, have demonstrated that the quantity, quality and spatial distribution of immune cells within the tumour has a greater prognostic value than the standard tumour staging based on tumour burden, infiltration of draining and regional lymph nodes by tumour cells, and evidence of metastases. This so-called "immunoscore" came to complete the immunoediting theory by increasing the knowledge of the immune events inside the tumours, and by better understanding, the immune architecture of these tumours, as well as the functional programs of their constituents, all of which complete the idea of how tumours evade from immunosurveillance. Forum of Clinical OncologyReinstating endogenous antitumor immunity: The concept of therapeutic management of cancer * E-mail: nfpist73@yahoo.gr However, a lot of cancer patients will fail to respond and therefore, it becomes crucial to identify biomarkers to predict who of the patients will most likely benefit from these therapies. Abstract: © De Gruyter Open Keywords: Cancer immunotherapy • Tumor infiltrating lymphocytes • Immunoscore • Cancer vaccines • Checkpoint inhibitors

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Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma

Abstract: Pembrolizumab and nivolumab monotherapies are effective therapies in ipilimumab-refractory metastatic melanoma and present an overall favorable toxicity profile.

Cited by 74 publications

References 32 publications

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology

Molecular Imaging of Immunotherapy Targets in Cancer

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

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