Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study

Mamot, Christoph; Ritschard, Reto; Wicki, Andreas; Stehle, Gregor; Dieterle, Thomas; Bubendorf, Lukas; Hilker, C.; Deuster, Stefanie; Herrmann, Richard; Rochlitz, Christoph

doi:10.1016/s1470-2045(12)70476-x

Cited by 212 publications

(118 citation statements)

References 17 publications

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“…Numerous targeted nanoparticles against different antigens have been described in the literature for potential treatment of solid tumors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The majority of those studies focused on the selection and design of nanoparticles and/or targeting moieties.…”

Section: Introductionmentioning

confidence: 99%

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Hendriks

Klinz

Reynolds

et al. 2013

Molecular Cancer Therapeutics

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Numerous targeted nanotherapeutics have been described for potential treatment of solid tumors. Although attention has focused on antigen selection and molecular design of these systems, there has been comparatively little study of how cellular heterogeneity influences interaction of targeted nanoparticles with tumor cells. Antigens, such as HER2/ERBB2, are heterogeneously expressed across different indications, across patients, and within individual tumors. Furthermore, antigen expression in nontarget tissues necessitates optimization of the therapeutic window. Understanding the performance of a given nanoparticle under different regimens of antigen expression has the ability to inform patient selection and clinical development decisions. In this work, HER2-targeted liposomal doxorubicin was used as a modeltargeted nanoparticle to quantitatively investigate the effect of HER2 expression levels on delivery of doxorubicin to the nucleus. We find quantitatively greater nuclear doxorubicin delivery with increasing HER2 expression, exhibiting a threshold effect at approximately 2 Â 10 5 HER2 receptors/cell. Kinetic modeling indicated that the threshold effect arises from multiple low-affinity interactions between the targeted liposome and HER2. These results support previous data showing little or no uptake into human cardiomyocytes, which express levels of HER2 below the threshold. Finally, these results suggest that HER2-targeted liposomal doxorubicin may effectively target tumors that fall below traditional definitions of HER2-positive tumors, thereby expanding the potential population of patients that might benefit from this agent. Mol Cancer Ther; 12(9); 1816-28. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Hendriks

Klinz

Reynolds

et al. 2013

Molecular Cancer Therapeutics

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“…However, active cellular targeting improve therapeutic efficacy by decreasing unspecificity and increasing uptake [74,75]. Moreover, decoration of nanocarriers with targeting moieties overcomes the multiple-drug resistance (MDR), using peptides, [76][77][78][79][80] and avoids the limitations of passive targeting, since the EPR effect is not produced in certain hypovascular tumors [81,82] and the permeability of blood vessels can vary in a single tumor [83].…”

Section: Reprinted By Permission From Macmillan Publishers Ltd: [Natumentioning

confidence: 99%

“…With respect to immunoliposomes, although many preclinical studies can be found in the literature [24,215,275,276] and a few clinical trials are in progress [18,75,[277][278][279] an siRNA that targets PKN3 [18,286], or TKM-PLK1 that includes siRNA against PLK1 for the treatment of neuroendocrine tumors and adrenocortical carcinomas (phase I/II clinical trials) [283,287,288]. The phase I liposomic formulation SGT-53 includes plasmidic DNA that expresses the tumor suppressor gene p53 to treat solid tumors [280,289].…”

Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,399

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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“…The majority of the clinically approved cancer nanomedicines are based on the concept of EPR, while some of them designed with ligand mediated active targeting to alter the behaviour in tumors are [203] in clinical trials, such as BIND-014 (Bind therapeutics), [211] MM-302 (Merrimack Pharmaceuticals), [212] and anti-EGFR immunoliposomes. [213] Recently, BIND-014, which is a tumor prostate-specific membrane antigen (PSMA)-targeted nanoparticle containing docetaxel, has shown disappointing results in Phase II clinical trials. Although, clinical results demonstrated the enhanced tumor accumulation with reduced side effects as compared to the free drugs, the higher drug concentration achieved was unable to provide better therapeutic efficacy.…”

Section: Cancer Nanomedicines From the Clinical Medicine Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study

Cited by 212 publications

References 17 publications

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

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