Reply to A. Indini et al

Horvat, Troy Z.; Adel, Nelly G.; Dang, Thu-Oanh; Momtaz, Parisa; Postow, Michael A.; Callahan, Margaret K.; Dickson, Mark A.; D’Angelo, Sandra P.; Woo, Kaitlin M.; Panageas, Katherine S.; Wolchok, Jedd D.; Chapman, Paul B.

doi:10.1200/jco.2015.65.7007

Cited by 6 publications

(8 citation statements)

References 9 publications

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“…Irreversible damage to endocrine organs during this period of inflammation could necessitate hormone supplementation (Dillard et al, 2010;Juszczak et al, 2012;Kaehler et al, 2009). In a single-institution experience with commercial use of ipilimumab, toxicities were very common, and more that 30% of patients treated with ipilimumab required immunosuppressant treatment (Horvat et al, 2015). CTLA-4 Blockade: Outside of Melanoma Ipilimumab has also been tested in several additional malignancies including prostate cancer, NSCLC, RCC, pancreatic cancer, and hematologic malignancies and has been largely disappointing.…”

Section: Introductionmentioning

confidence: 99%

Targeting T Cell Co-receptors for Cancer Therapy

2016

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Checkpoint-blocking antibodies can generate potent anti-tumor responses by encouraging the immune system to seek and destroy cancer cells. At this time, the United States Food and Drug Administration has approved three checkpoint-blocking antibodies in three disease indications, and additional approvals are expected to broaden the clinical scope of immunotherapy. Herein, we review the clinical development of CTLA-4-, PD-1-, and PD-L1-blocking antibodies across tumor types and briefly discuss areas of active investigation of potential biomarkers.

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Section: Introductionmentioning

confidence: 99%

Targeting T Cell Co-receptors for Cancer Therapy

2016

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“…In the past few decades, cancer therapy has advanced, with immuno-oncology emerging as an effective strategy for a variety of advanced-stage cancers (Horvat et al 2015). There are a number of modalities of immunotherapy, including monoclonal antibodies (mAbs), adoptive cell therapy, immunomodulatory small molecules, oncolytic viruses, vaccines and tumor-targeting mAbs.…”

Section: Introductionmentioning

confidence: 99%

“…Data published with melanoma patients also report that overall survival and time to treatment failure were not affected by the occurrence of irAEs or the need for systemic corticosteroids (Horvat et al 2015). Most irAEs occur within 3-6 months of initiation of immunotherapy, although a delayed effect of immune checkpoint antibodies cannot be ruled out, sometimes up to few years after the start of treatment (Michot et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Endocrine side effects of cancer immunotherapy

Cukier¹,

Santini²,

Scaranti³

et al. 2017

Endocrine-Related Cancer

144

114

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Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.

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“…For example, the CTLA-4 gene was cloned initially from CD8 + T cells in mice [67]. However, contrary to an earlier report [42] studies in humans revealed significantly higher expression of the inhibitory receptor in CD4 + T cells compared to the cytotoxic effector T cells [68]. Hence, receptor blockade is likely to have a significant influence on cytotoxic T cell-mediated anti-tumor effect [73,74].…”

Section: Off-target Effectsmentioning

confidence: 97%

“…The suppressive effect of the latter is a biological version of yin and yang whereby protection is binary; one against autoantigen [38], the other against the antitumor effect. Although conflicting data have been published, the relevance and role of CTLA-4 and T reg cells in these two "protective" outcomes may be inherent in the correlation some investigators have found between incident ir-AEs and improved tumor outcomes [39][40][41][42].…”

Section: Off-target Effectsmentioning

confidence: 99%

Evolution of Cancer, Adaptive Immunity, and Immunotherapy

Smith¹

2019

J. Anal. Oncol.

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The first clinical trials to investigate the efficacy of immunotherapy in cancer were problematic because of issues related to product availability, cost, and purity. Moreover, these factors could have contributed to the modest efficacy of these agents. The ability to clone specific genes coupled with the development of recombinant DNA technology removed some major barriers such that only 20 years later, approval of the first engineered monoclonal antibody (mAb) for clinical use occurred with practice-changing implications. Subsequent to rituximab, more than 30 additional mAbs have indications for a number of hematologic malignancies and solid tumors. Indeed, the application of adaptive immunity is now an integral component of therapy for many cancers. This paper delves into the complex science of immunology by investigating how the term evolution is applicable to tumorigenesis, the adaptive immune response, and cancer therapy.

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Reply to A. Indini et al

Cited by 6 publications

References 9 publications

Targeting T Cell Co-receptors for Cancer Therapy

Targeting T Cell Co-receptors for Cancer Therapy

Endocrine side effects of cancer immunotherapy

Evolution of Cancer, Adaptive Immunity, and Immunotherapy

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