Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment

Capdevila, Jaume; Élez, Elena; Macarulla, Teresa; Ramos, Francisco Javier; Ruiz-Echarri, Manuel; Tabernero, Josep

doi:10.1016/j.ctrv.2009.02.001

Cited by 116 publications

(114 citation statements)

References 66 publications

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“…It has been shown to have an important function in the growth and survival of tumor cells, including processes such as cellular growth, apoptosis, metastasis, and angiogenesis (Zhang et al, 2007;Capdevila et al, 2009). We have found that PA-MSHA preferentially inhibited the proliferation of breast cancer cell lines, which are all EGFR-positive.…”

Section: Introductionmentioning

confidence: 80%

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

Liu

Hou

Zhu³

et al. 2010

Oncogene

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To identify more therapeutic targets and clarify the detailed mechanisms of Pseudomonas aeruginosa-mannosesensitive hemagglutinin (PA-MSHA) on breast cancer cells both in vitro and in vivo. PA-MSHA was administered to epidermal growth factor receptor (EGFR)-positive human breast cancer cell lines MDA-MB-231HM and MDA-MB-468 in vitro and to mice bearing tumor xenografts. The mannose cocultured test was used to detect the effect of mannose on PA-MSHA-induced cell proliferation, cell cycle arrest, apoptosis, and EGFR pathway signaling. We found that cells stimulated with PA-MSHA exhibited a downregulation of EGFR signaling. The addition of mannose partially inhibited the PA-MSHA-stimulated cell anti-proliferative effect, cell apoptosis, cell cycle arrest, activation of apoptosis-associated caspases, and even downregulation of the EGFR signaling pathway. In vivo, PA-MSHA treatment significantly suppressed mammary tumorigenesis in xenografts in mice and decreased lung metastasis in MDA-MB-231HM celltransplanted mice. Tumor sample analyses confirmed inhibition of the EGFR pathway in the PA-MSHAtreated mice. In conclusion, this study showed that the involvement of the mannose-mediated EGFR pathway has a critical function in the preclinical rationale for the development of PA-MSHA for the treatment of human breast cancer. It also suggests the potentially beneficial use of PA-MSHA in adjuvant therapy for breast tumors with EGFR overexpression.

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Section: Introductionmentioning

confidence: 80%

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

Liu

Hou

Zhu³

et al. 2010

Oncogene

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“…2,11,12 Panitumumab is a human IgG2k mAb that binds specifically to EGFR with high affinity, and not to the other ErbB family members. 13,14 Treatment with panitumumab has been associated with low immunogenicity and low risk of hypersensitivity reactions. 15,16 More importantly, cetuximab-resistant patients who harbor the S492R mutation responded to treatment with panitumumab.…”

Section: Introductionmentioning

confidence: 99%

Generation and characterization of a target-selectively activated antibody against epidermal growth factor receptor with enhanced anti-tumor potency

Yang

Guo

Mao³

et al. 2015

mAbs

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These authors contributed equally to this work.Keywords: monoclonal antibody, EGFR, panitumumab, ADCC, target-selective activation, Probody TM Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; mAb, monoclonal antibody; EGFR, epidermal growth factor receptor; uPA, urokinase-type plasminogen activator; TKI, tyrosine kinase inhibitor; IgG, Immunoglobulin G; ELISA, enzyme-linked immunosorbent assay; SPR, surface plasmon resonance; CI, confidence interval; LC, light chain; HC, heavy chain; EGFR VIII, EGFR Type III Variant; CRC, colorectal cancer; ECD, extracellular domain; SEC, size exclusion chromatography; CCK-8, Cell Counting Kit 8YunPanitumumab, as a commercially available antibody, is an effective anticancer therapeutic against epidermal growth factor receptor (EGFR), although it exerts weak antibody-dependent cell-mediated cytotoxicity (ADCC) activity owing to its IgG2 nature. Here, we firstly engineered panitumumab by grafting its variable region into an IgG1 backbone. The engineered panitumumab (denoted as Pan) retained binding activity identical to the parental antibody while exhibiting stronger ADCC activity in vitro and more potent antitumor effect in vivo. To further enhance the target selectivity of Pan, we generated Pan-P by tethering an epitope-blocking peptide to Pan via a tumor-specific protease selective linker. Pan-P showed almost 40-fold weaker affinity compared with Pan, but functional activity was restored to a similar extent as Pan when Pan-P was selectively activated by urokinase-type plasminogen activator (uPA). More importantly, targeted localization of Pan-P was observed in tumor samples from colorectal cancer (CRC) patients and tumor-bearing nude mice, strongly indicating that specific activation also existed ex vivo and in vivo. Furthermore, Pan-P also exhibited effective in vivo antitumor potency similar to Pan. Taken together, our data evidence the enhanced antitumor potency and excellent target selectivity of Pan-P, suggesting its potential use for minimizing on-target toxicity in anti-EGFR therapy.

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“…Expression of EGFR varies widely in a variety of tumors, including head and neck (80-100%), renal (50-90%), lung (40-80%), breast (14-90%), colorectal (25-77%), ovarian (25-70%), prostate (39-47%), glioma (40-63%), pancreas (30-50%) and bladder (31-48%) (Herbst and Shin, 2002;Capdevila et al, 2009). High levels of EGFR expression in tumors have been correlated with aggressiveness of disease, poor prognosis and decreased survival, poor response to therapy and the development of resistance to cytotoxic agents in some tumor types (Brabender et al, 2001;Capdevila et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Conversion of a murine monoclonal antibody A13 targeting epidermal growth factor receptor to a human monoclonal antibody by guided selection

et al. 2012

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Abbreviations: HAMA, human anti-mouse antibody; scFv, single chain Fv; VH, variable region of immunoglobulin heavy chain; VL, variable region of immunoglobulin light chain AbstractEpidermal growth factor receptor (EGFR) is an attractive target for tumor therapy because it is overexpressed in the majority of solid tumors and the increase in receptor expression levels has been linked with a poor clinical prognosis. Also it is well established that blocking the interaction of EGFR and the growth factors could lead to the arrest of tumor growth and possibly result in tumor cell death. A13 is a murine monoclonal antibody (mAb) that specifically binds to various sets of EGFR-expressing tumor cells and inhibits EGF-induced EGFR phosphorylation. We isolated human immunoglobulin genes by guided selection based on the mAb A13. Four different human single chain Fvs (scFvs) were isolated from from hybrid scFv libraries containing a human V H repertoire with the V L of mAb A13 and a human VL repertoire with the VH of mAb A13. All the 4 scFvs bound to EGFR-expressing A431 cells. One scFv (SC414) with the highest affinity was converted to IgG1 (ER414). The ER414 exhibited ∼17 fold lower affinity compared to the A13 mAb. In addition the ER414 inhibited an EGF-induced tyrosine phosphorylation of EGFR with much lower efficacy compared to the A13 mAb and Cetuximab (Merck KgaA, Germany). We identified that the epitope of A13 mAb is retained in ER414. This approach will provide an efficient way of converting a murine mAb to a human mAb.

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Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment

Cited by 116 publications

References 66 publications

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

Generation and characterization of a target-selectively activated antibody against epidermal growth factor receptor with enhanced anti-tumor potency

Conversion of a murine monoclonal antibody A13 targeting epidermal growth factor receptor to a human monoclonal antibody by guided selection

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