Product review on the Anti-PD-L1 antibody atezolizumab

Shah, Neil; Kelly, William; Liu, Stephen V.; Choquette, Karin; Spira, Alexander I.

doi:10.1080/21645515.2017.1403694

Cited by 44 publications

(37 citation statements)

References 81 publications

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“…Overall, the objective response rate was 48%; however, it was higher in patients with PDL-1 expression (IC 2/3). Similarly, OS was 11.4 months versus 6.5 months when comparing PDL-1 expression (IC 2/3 vs. IC 0), with the benefit favoring the use of atezolizumab 35 .…”

Section: Atezolizumabmentioning

confidence: 95%

“…There are numerous Phase I/II trials, in which the usefulness of this molecule has been assessed in several neoplasms such as NSCSC, including BIRCH, FIR, POPLAR, and OAK, the latter being a Phase III, and IMVIGOR 210 a Phase II study on bladder cancer. In all these studies, atezolizumab was administered at a fixed dose of 1200 mg IV every 21 days 35 . Thus, the OAK study 36 , in a Phase III clinical trial randomized 850 patients diagnosed with Stage IIIB or IV NSCLC with progression to 1 or 2 previous lines of treatment and who met eligibility criteria, received atezolizumab 1200 mg versus docetaxel 75 mg/m 2 every 3 weeks.…”

Section: Atezolizumabmentioning

confidence: 99%

“…This trial had two analysis cohorts. The first cohort included patients who were not candidates for platinum therapy, with a benefit in objective response rates of 23% and a median OS of 15.9 months regardless of the degree of PDL-1 expression, with adequate treatment tolerance and manageable AEs 35 .…”

Section: Atezolizumabmentioning

confidence: 99%

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Immunotherapy Treatment Against Cervical Cancer

Jiménez-Lima¹,

Arango-Bravo²,

Galicia-Carmona³

et al. 2020

RIC

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Cervical cancer (CC) is one of the most common gynecological tumors and an important health problem, especially in developing countries. The vast majority of patients in early stages are cured of the disease with surgical treatment and with concomitant chemoradiotherapy in locally advanced stages. However, in patients with recurrent, persistent, or metastatic cervical CC, the effectiveness of treatment is limited, except for the combination of chemotherapy based on platinum doublets plus bevacizumab, the treatment that has achieved the best results to date. Programmed cell death-1/PD ligand-1 (PD-1/PD-L1) inhibitors could be a novel and cutting-edge therapeutic option to improve clinical outcomes in this group of patients. Thus far, there are a few Phase I/II clinical trials that have assessed the usefulness of pembrolizumab and nivolumab in this group of patients; these include the KEYNOTE 028, KEYNOTE 158, and CHECKMATE 358 trials, in which clinical benefit has been proven with PD-1/PD-L1 inhibitors in recurrent, persistent, or metastatic CC, as second-line treatment. There are also some ongoing trials that could provide further evidence on the PD-1/PD-L1 pathway as a therapeutic target in CC. In this review, we will focus on the usefulness of these PD-1/PDL1 inhibitors in CC, as well as on trials that are still in the recruitment phase, to confirm their effectiveness in this clinical setting.

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Section: Atezolizumabmentioning

confidence: 95%

Section: Atezolizumabmentioning

confidence: 99%

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Immunotherapy Treatment Against Cervical Cancer

Jiménez-Lima¹,

Arango-Bravo²,

Galicia-Carmona³

et al. 2020

RIC

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“…The threshold selection seems to be tumor-type dependent, i.e., high (>50%) for non-small-cell lung cancer (NSCL) and low (>1%) for the other types. For Atezolizumab, during clinical trials different positivity thresholds of PD-L1 expression were tested too, ranging from >1% to >50% [ 29 ]. For Durvalumab, a clinical trial NCT01693562 in NSCLC suggests that patient who had detectable levels of PD-L1 expression over 25% on tumor cells may have longer survival [ 30 ].…”

Section: Pd1 and Pd-l1: Wish You Were Herementioning

confidence: 99%

Like a Rolling Stone: Sting-Cgas Pathway and Cell-Free DNA as Biomarkers for Combinatorial Immunotherapy

Sicard

Fina²,

Fanciullino

et al. 2020

Pharmaceutics

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Combining immune checkpoint inhibitors with other treatments likely to harness tumor immunity is a rising strategy in oncology. The exact modalities of such a combinatorial regimen are yet to be defined, and most attempts have relied so far on concomitant dosing, rather than sequential or phased administration. Because immunomodulating features are likely to be time-, dose-, and-schedule dependent, the need for biomarkers providing real-time information is critical to better define the optimal time-window to combine immune checkpoint inhibitors with other drugs. In this review, we present the various putative markers that have been investigated as predictive tools with immune checkpoint inhibitors and could be used to help further combining treatments. Whereas none of the current biomarkers, such as the PDL1 expression of a tumor mutational burden, is suitable to identify the best way to combine treatments, monitoring circulating tumor DNA is a promising strategy, in particular to check whether the STING-cGAS pathway has been activated by cytotoxics. As such, circulating tumor DNA could help defining the best time-window to administrate immune checkpoint inhibitors after that cytotoxics have been given.

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“…As PD-L1 knockdown does not represent a current clinical scenario in patients, we next evaluated a clinical grade PD-L1 blocking antibody, atezolizumab 61 . Again, naïve and activated T cells were cultured with control or chemerin-treated DU145 cells.…”

Section: Chemerin Treatment Is As Effective As Atezolizumab At Augmenmentioning

confidence: 99%

Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis

Rennier

Krug

Virdi

et al. 2019

Preprint

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Chemerin (RARRES2) is an endogenous leukocyte chemoattractant known to recruit innate immune cells through its chemotactic receptor, CMKLR1. RARRES2 is often downregulated in prostate cancer and across multiple tumor types compared to normal tissue. Additionally, a methylome-wide analysis identified RARRES2 as one of the most hypermethylated genes in sarcoma. Recent studies have shown that augmenting chemerin in the tumor microenvironment significantly suppresses tumor growth, at least in part by recruitment of immune effector cells. However, as tumor cells have been shown to express functional chemokine receptors that can impact their phenotype, we hypothesized that chemerin might have additional, tumor-intrinsic effects. Here, we show for the first time that human cancer cells exposed to exogenous chemerin significantly upregulate PTEN expression and activity. Additionally, chemerin-induced PTEN expression correlated with a concomitant reduction in PD-L1 mRNA and protein expression. Chemerin treatment of tumor cells led to significantly reduced tumor cell migration/invasion, as well as significantly increased cytotoxicity by T cells. siRNA knockdown of tumor expressed CMKLR1 abrogated chemerin-induced modulation of PTEN and PD-L1 expression and activity, supporting the presence of a CMKLR1/PTEN/PD-L1 signaling cascade. We then compared chemerin treatment to PD-L1 inhibition by siRNA knockdown or the antagonistic antibody atezolizumab in T cell cytotoxicity assays and surprisingly found chemerin treatment was as effective as both Chemerin modulates PTEN/PD-L1 via CMKLR1 in human tumors Page 2 of 29 PD-L1 knockdown and atezolizumab treatment in mediating tumor lysis. Collectively, our data show a novel link between chemerin, PTEN and PD-L1 in human tumor lines, with functional consequences that may have a role in improving T cell-mediated immunotherapies. Runnning Title: Chemerin modulates PTEN/PD-L1 via CMKLR1 in human tumors Word Counts: Abstract -250

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Product review on the Anti-PD-L1 antibody atezolizumab

Cited by 44 publications

References 81 publications

Immunotherapy Treatment Against Cervical Cancer

Immunotherapy Treatment Against Cervical Cancer

Like a Rolling Stone: Sting-Cgas Pathway and Cell-Free DNA as Biomarkers for Combinatorial Immunotherapy

Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis

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