Therapeutic targets and new directions for antibodies developed for ovarian cancer

Bax, Heather J.; Josephs, Debra H.; Pellizzari, Giulia; Spicer, James; Montes, Ana; Karagiannis, Sophia N.

doi:10.1080/19420862.2016.1219005

Cited by 16 publications

(11 citation statements)

References 157 publications

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“…We evaluated basophils from patients who had been previously treated with targeted anti-cancer therapies: (i) the anti-VEGF mAb bevacizumab [ 47 , 48 , 49 ] ( n = 9), the only antibody approved for the treatment of ovarian cancer, and the administration of which has been reported to trigger hypersensitivity [ 48 , 49 , 50 ]; (ii) the poly-ADP ribose polymerase (PARP) inhibitors olaparib ( n = 1) and niraparib [ 51 , 52 , 53 ] ( n = 1); (iii) the anti-PD-L1 mAb avelumab [ 47 ] ( n = 2). In all patient samples, basophils were identified ( Figure 4 A and Figure S5A ) and retained capacity to be stimulated with anti-FcεRI, anti-IgE, and fMLP to an equivalent degree to that observed in patients who had not previously received targeted therapies ( Figure 4 B,C and Figure S5B, Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Bax

Chauhan

Stavraka

et al. 2020

Cells

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Basophils are involved in manifestations of hypersensitivity, however, the current understanding of their propensity for activation and their prognostic value in cancer patients remains unclear. As in healthy and atopic individuals, basophil populations were identified in blood from ovarian cancer patients (n = 53) with diverse tumor histologies and treatment histories. Ex vivo basophil activation was measured by CD63 expression using the basophil activation test (BAT). Irrespective of prior treatment, basophils could be activated by stimulation with IgE- (anti-FcεRI and anti-IgE) and non-IgE (fMLP) mediated triggers. Basophil activation was detected by ex vivo exposure to paclitaxel, but not to other anti-cancer therapies, in agreement with a clinical history of systemic hypersensitivity reactions to paclitaxel. Protein and gene expression analyses support the presence of basophils (CCR3, CD123, FcεRI) and activated basophils (CD63, CD203c, tryptase) in ovarian tumors. Greater numbers of circulating basophils, cells with greater capacity for ex vivo stimulation (n = 35), and gene signatures indicating the presence of activated basophils in tumors (n = 439) were each associated with improved survival in ovarian cancer. Circulating basophils in cancer patients respond to IgE- and non-IgE-mediated signals and could help identify hypersensitivity to therapeutic agents. Activated circulating and tumor-infiltrating basophils may be potential biomarkers in oncology.

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Section: Resultsmentioning

confidence: 99%

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Bax

Chauhan

Stavraka

et al. 2020

Cells

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“…The “TNF network” plays a paracrine role in angiogenesis, myeloid cell infiltration and NOTCH signaling in both a mouse model and human ovarian cancer specimens 30 , and inhibition of the “TNF network” in the mouse model confirmed this conclusion. An elevated level of IL-6 in ascites and serum of ovarian cancer is associated with the generation of TAMs 10 and the reduction of apoptotic signal sensitivity and angiogenesis 31 , which promote cancer progression directly. CXCR4 is constitutively expressed in ovarian cancer, and CXCL12 has been found to be highly concentrated in ascites of ovarian cancer.…”

Section: Tumor-associated Macrophages (Tams)mentioning

confidence: 99%

Immune Cell Population in Ovarian Tumor Microenvironment

Cai¹,

Jin²

2017

J. Cancer

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Ovarian cancer, the third most common with highest mortality rates gynecological malignancy among women in China, is characterized by a unique tumor immune microenvironment. Immune-cell population infiltrated into the tumor tissue among patients with ovarian cancer are associated positively or negatively with antitumor activity. The imbalance between immune activation and immune suppression can result in oncogenesis and cancer progression. Therefore, intense investigation of the immunologic mechanism of ovarian cancer is urgently needed, and a comprehensive understanding of the network in which immune cells interact with the microenvironment, tumor cells and each other will greatly promote the development of more effective immunotherapies for ovarian cancer. In this review, we will focus on the main immune-cell population in ovarian tumor microenvironment, discuss their role in tumor progression and try to give the readers a new perspective in finding more promising therapeutic targets for cancers.

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“…Both anti-PD-L1 (nivolumab, pembrolizumab, avelumab) and anti-CTLA4 (ipilimumab) have been tested in phase I or phase II clinical trials, with objective response rates about 15% and some stable response. Currentl, some phase III clinical trials are ongoing with avelumab (53,54).…”

Section: Immunotherapymentioning

confidence: 99%

Ovarian Cancer Management in the Oldest Old: Improving Outcomes and Tailoring Treatments

Tortorella¹,

Vizzielli²,

Fusco³

et al. 2017

Aging and disease

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Ovarian cancer is the most common cause of death from gynecological cancers in developed countries. It is a common disease of older women at or above 63 years upon diagnosis. Thanks to advance in new treatments, mortality from ovarian cancer has declined in developed countries in the last decade. This decline in mortality rate is unevenly distributed across the age-spectrum. While mortality in younger women has decreased 21.7%, for elderly women it has declined only 2.2%. Even if ovarian cancer is clearly a disease of the elderly, older women are underrepresented in clinical trials, and scant evidence exists for the treatment of women older than 80 years. Moreover, older women are frequently undertreated, receive less chemotherapy and less combination of surgery and chemotherapy, despite the fact that this is considered the optimal treatment modality. This may be mainly due to the lack of evidence and physician’s confidence in the management of elderly women with ovarian cancer. In this review, we focus on the management of older women with ovarian cancer, considering geriatric features tied to this population.

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Therapeutic targets and new directions for antibodies developed for ovarian cancer

Cited by 16 publications

References 157 publications

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Basophils from Cancer Patients Respond to Immune Stimuli and Predict Clinical Outcome

Immune Cell Population in Ovarian Tumor Microenvironment

Ovarian Cancer Management in the Oldest Old: Improving Outcomes and Tailoring Treatments

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