Targeting human epidermal growth factor receptor 2 by a cell-penetrating peptide–affibody bioconjugate

Govindarajan, Srinath; Jeyarajan, Sivakumar; Garimidi, Prathyusha; Rangaraj, Nandini; Kumar, Jerald Mahesh; Rao, Nalam Madhusudhana; Gopal, Vijaya

doi:10.1016/j.biomaterials.2011.12.003

Cited by 60 publications

(29 citation statements)

References 47 publications

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“…Specifically, as previously presented in gene therapy studies, prediction models for drug diffusion within the tumor have to be established before initiation of drug administration 67. The ITASSER ([http://zhanglab.ccmb.med.umich.edu], Ann Arbor, MI, USA) software is an established evaluation method with many applications that has been used in previous studies 67,68…”

Section: Discussionmentioning

confidence: 99%

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Hohenforst-Schmidt¹,

Zarogoulidis²,

Darwiche³

et al. 2013

DDDT

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Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.

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Section: Discussionmentioning

confidence: 99%

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Hohenforst-Schmidt¹,

Zarogoulidis²,

Darwiche³

et al. 2013

DDDT

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“…30,55 In our earlier work, we have demonstrated that tumor regression was achieved by Affibody conjugates only on tumors that were generated from EGFR-positive cell line (MDA-MB-453) and not on tumors generated by EGFR-negative cell lines (MDA-MB-231). 34 In the same study, the inhibitory role of free Affibody in inhibiting gene expression by an Affibody-mediated formulation was also demonstrated. The effect of Affibody conjugation compared to free PS and (PS-dendrimer) DPN is more significant in in vitro cell-based studies.…”

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confidence: 84%

“…Abundance of HER2 in SK-OV-3 cells and its absence in MCF-7 cells were earlier demonstrated by Western blot using HER2 (ERBB2) antibodies. 34 In the PDT studies, each of the treatments was performed in triplicate and in two identical sets. One set was subjected to exposure to light, and another set was protected even from stray light and was treated as a dark control.…”

Section: Light-mediated Cell Death In the Presence Of Pamam Dendrimersmentioning

confidence: 99%

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Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Amreddy

Vijayashree

Adimoolam

et al. 2015

IJN

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Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21 H ,23 H -porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

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“…Novel avenues such as ERBB2-specific tyrosine kinase inhibitors (i.e. emodin) (Schroeder et al 2014), ERBB2-targeting antisense oligonucleotides (Han et al 2013) and rationally designed anti-ERBB2 peptide mimetics (Govindarajan et al 2012) are also undergoing different stages of clinical trials (Figure 1). The limitations of chemotherapy and radiation include the fact that they not only affect cancerous cells, but also target all actively dividing healthy cells.…”

Section: Introductionmentioning

confidence: 99%

Overcoming the Challenge of Transduction of Human T-cells with Chimeric Antigen Receptor (CAR) Specific for ERBB2 Antigen

Munisvaradass¹,

Ding²,

Koh³

et al. 2017

JSM

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were isolated from the peripheral blood mononuclear cells (PBMCs). The constructed CAR gene was inserted into a lentiviral plasmid containing the green fluorescent protein (GFP) tag and lentiviral particles were produced. These lentiviral particles were used to transduce activated T-cells by spinoculation. T-cells were activated using Dynabeadconjugated CD3/CD28 human T-cell activator and interleukin-2 (IL-2) before transduction. CD3+ T-cells were selected and GFP expression, which indicated transduction, was observed. Future studies will focus on in vitro and in vivo models to determine the efficiency of CAR-T cells in specifically targeting ERBB2-expressing cells. Keywords: Breast cancer; CD3+ T-cells; chimeric antigen receptor (CAR); immunotherapy ABSTRAK Kanser payudara adalah salah satu kanser yang kerap melanda kaum wanita. Kajian saintifik telah mengaitkan lebihan ekspresi antigen ERBB2 pada barah kanser yang lebih agresif. Untuk menangani masalah ini, teknologi reseptor kimera antigen (CAR) boleh digunakan. Untuk ini, sel T manusia ditransduksi dengan urutan gen pengekodan CAR yang khusus untuk antigen berkaitan-barah (TAA). Sel T yang ditransduksi dengan CAR (CAR-T) secara genetik dapat mensasar kepada antigen kanser tanpa memerlukan pengenalan kompleks kehistoserasian utama (MHC), menjadikan ia pilihan terapi imun berpotensi umum. Walau bagaimanapun, transduksi gen terapeutik ke dalam sel T manusia dan pengembangan

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Targeting human epidermal growth factor receptor 2 by a cell-penetrating peptide–affibody bioconjugate

Cited by 60 publications

References 47 publications

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Overcoming the Challenge of Transduction of Human T-cells with Chimeric Antigen Receptor (CAR) Specific for ERBB2 Antigen

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