Structure and Optimization of Checkpoint Inhibitors

Picardo, Sarah; Doi, Jeffrey; Hansen, Aaron R.

doi:10.3390/cancers12010038

Cited by 39 publications

(33 citation statements)

References 104 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nivolumab, also an IgG4 antibody, is very similar in structure to pembrolizumab, except that nivolumab binds to the N-terminal loop on the PD-1 molecule, while pembrolizumab binds to the C’D loop. 24 The phase III ATTRACTION-2 (ONO-4538-12) trial compared nivolumab with a placebo in 493 Asian patients with unresectable or recurrent GC that was refractory to or intolerant of at least two previous standard chemotherapy regimens. 5 The results showed a significantly prolonged OS for the nivolumab group with a 1-year OS rate of 27.3% vs 11.6%.…”

Section: Introductionmentioning

confidence: 99%

“… 28 There are some differences between PD-1 inhibition and PD-L1 inhibition, as PD-1 targeting therapeutic antibodies including pembrolizumab and nivolumab block the PD-1/PD-L1 or PD-1/PD-L2 interaction to restore tumor-specific T-cell reactivity without mediating ADCC. 24 The JAVELIN Gastric 300 trial, the ﬁrst study to compare avelumab with standard chemotherapy in third-line treatment for GC, did not achieve its primary end point of improving OS or the secondary end points of PFS and ORR. 18 This negative finding may be attributed to the usage of the active comparator in the control arm.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

Kang

Chau

2020

ESMO Open

View full text Add to dashboard Cite

Immunotherapy is revolutionising cancer treatment and has already emerged as standard treatment for patients with recurrent or metastatic gastric cancer (GC). Recent research has been focused on identifying robust predictive biomarkers for GC treated with immune checkpoint inhibitors (ICIs). The expression of programmed cell death protein-ligand-1 (PD-L1) is considered a manifestation of immune response evasion, and several studies have already reported the potential of PD-L1 expression as a predictive parameter for various human malignancies. Meanwhile, based on comprehensive molecular characterisation of GC, testing for Epstein-Barr virus and microsatellite instability is a potential predictive biomarker. Culminating evidence suggests that novel biomarkers, such as the tumour mutational burden and gene expression signature, could indicate the success of treatment with ICIs. However, the exact roles of these biomarkers in GC treated with ICIs remain unclear. Therefore, this study reviews recent scientific data on current and emerging biomarkers for ICIs in GC, which have potential to improve treatment outcomes.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

Kang

Chau

2020

ESMO Open

View full text Add to dashboard Cite

show abstract

“…One such method is using pre-drug formulations, where the antibody becomes active only after reaching the tumor site. Promising results have already been shown in the case of ipilimumab [33]. However, as previously mentioned, the discovery of biomarkers for accurate irAE risk prediction is of utmost importance and would greatly improve patients' quality of life and survival.…”

Section: Adverse Events From Immune Checkpoint Inhibitors In Dmmr Mcrcmentioning

confidence: 99%

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis

Mavroudis

Sfakianaki

et al. 2020

Cancers

View full text Add to dashboard Cite

Immunotherapy has considerably increased the number of anticancer agents in many tumor types including metastatic colorectal cancer (mCRC). Anti-PD-1 (programmed death 1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitors (ICI) have been shown to benefit the mCRC patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, ICI is not effective in mismatch repair proficient (pMMR) colorectal tumors, which constitute a large population of patients. Several clinical trials evaluating the efficacy of immunotherapy combined with chemotherapy, radiation therapy, or other agents are currently ongoing to extend the benefit of immunotherapy to pMMR mCRC cases. In dMMR patients, MSI testing through immunohistochemistry and/or polymerase chain reaction can be used to identify patients that will benefit from immunotherapy. Next-generation sequencing has the ability to detect MSI-H using a low amount of nucleic acids and its application in clinical practice is currently being explored. Preliminary data suggest that radiomics is capable of discriminating MSI from microsatellite stable mCRC and may play a role as an imaging biomarker in the future. Tumor mutational burden, neoantigen burden, tumor-infiltrating lymphocytes, immunoscore, and gastrointestinal microbiome are promising biomarkers that require further investigation and validation.

show abstract

“…Durvalumab is a monoclonal antibody that block PD-L1 [74,117]. Tremelimumab is a monoclonal antibody targeting CTLA-4 [118]. Durvalumab with tremelimumab showed a manageable tolerability profile, with antitumor activity irrespective of PD-L1 status, in patients with NSCLC in a phase 1b study [119].…”

Section: Negative Immunotherapy Studiesmentioning

confidence: 99%

First line Immunotherapy for Non-Small Cell Lung Cancer

2020

View full text Add to dashboard Cite

Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 < 50% are candidates for immunotherapy with pembrolizumab as a single agent if PL-1 > 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

show abstract

Structure and Optimization of Checkpoint Inhibitors

Cited by 39 publications

References 104 publications

Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

First line Immunotherapy for Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About