Dataset Information

Glyco-engineered anti-EGFR mAb elicits ADCC by NK cells from colorectal cancer patients irrespective of chemotherapy.

ABSTRACT: The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC), and is correlated with poor prognosis, making it an attractive target for monoclonal antibody (mAb) therapy. A component of the therapeutic efficacy of IgG1 mAbs is their stimulation of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells bearing the CD16 receptor. As NK cells are functionally impaired in cancer patients and may be further compromised upon chemotherapy, it is crucial to assess whether immunotherapeutic strategies aimed at further enhancing ADCC are viable.CRC patients before, during and after chemotherapy were immunophenotyped by flow cytometry for major white blood cell populations. ADCC-independent NK cell functionality was assessed in cytotoxicity assays against K562 cells. ADCC-dependent killing of EGFR(+) A431 cancer cells by NK cells was measured with a degranulation assay where ADCC was induced by GA201, an anti-EGFR mAb glyco-engineered to enhance ADCC.Here, we confirm the observation that NK cells in cancer patients are dysfunctional. However, GA201 was able to induce robust NK cell-dependent cytotoxicity in CRC patient NK cells, effectively overcoming their impairment.These findings support the evaluation of the therapeutic potential of GA201 in combination with chemotherapy in CRC patients.

SUBMITTER: Oppenheim DE

PROVIDER: S-EPMC3950873 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis.RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts. The pooled hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS), and pooled odds ratios (OR) for the overall response rate (ORR) were calculated by Review Manager 5.3.The results indicated that the addition of anti-EGFR mAbs to FOLFOX regimen in RAS wild-type mCRC patients for the first-line treatment resulted in considerable improvements in PFS (HR?=?0.70; 95% confidence interval [CI]: 0.59-0.82; P?<?.0001), OS (HR?=?0.79; 95%CI: 0.67-0.92; P?=?.003), and ORR (OR?=?2.56; 95% CI: 1.77-3.70; P?<?.00001) compared with chemotherapy alone. However, in RAS/BRAF wild patients, no significant differences were observed when anti-EGFR mAb was added to FLOX or XELOX regimen compared with chemotherapy alone with regard to OS and PFS, whereas FOLFOX+anti-EGFR mAb showed a marked superior OS and PFS (OS, HR?=?0.77; 95% CI: 0.61-0.98; P?=?.03; PFS, HR?=?0.68; 95% CI: 0.57-0.82; P?<?.00001). A meta-analysis including TAILOR and PRIME study suggests that primary tumor location (PTL) predicted a survival benefit when adding the EGFR antibody to FOLFOX regimen in RAS-wild mCRC patients (OS, HR for left-sided: 0.71; 95% CI: 0.59-0.85; P?=?.0002 and HR for right-sided: 0.90; 95% CI: 0.65-1.25; P?=?.53). However, the HR for PFS and ORR still suggests a benefit from the addition of anti-EGFR mAb in right-sided mCRC patients.So these results suggest anti-EGFR mAb and oxaliplatin are good partners in the FOLFOX regimen. The addition of EGFR antibody to FOLFOX markedly improved efficacy in RAS-wild patients with left-sided mCRC. In RAS/BRAF-wild patients, the efficacy is similar. For patients with right-sided tumor, a benefit showing a trendency in favor of anti-EGFR mAb can still seen. The molecular characteristics behind the tumor location need to be more explored urgently.

Dataset Information

Glyco-engineered anti-EGFR mAb elicits ADCC by NK cells from colorectal cancer patients irrespective of chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets