Production, Novel Assay Development and Clinical Applications of Monoclonal Antibodies

Chiarella, Pieranna

doi:10.2174/157489211795328549

Cited by 10 publications

(5 citation statements)

References 64 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The availability of these synthetic proteins has lead to the creation of numerous new diagnostic applications and clear improvements in those already existing (3). Immunofluorescence, immunohistochemistry, or epitopespecific immunoblotting are only a few examples of the current techniques based on mAbs.…”

Section: Introductionmentioning

confidence: 99%

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Torino

Barnabei

Paragliola

et al. 2013

European Journal of Endocrinology

108

103

View full text Add to dashboard Cite

mAbs are established targeted therapies for several diseases, including hematological and solid malignancies. These agents have shown a favorable toxicity profile, but, despite their high selectivity, new typical side-effects have emerged. In cancer patients, pituitary dysfunction may be mainly due to brain metastases or primary tumors and to related surgery and radiotherapy. Anticancer agents may induce hypopituitarism in patients cured for childhood cancers. These agents infrequently affect pituitary function in adult cancer patients. Notably, hypophysitis, a previously very rare disease, has emerged as a distinctive side-effect of ipilimumab and tremelimumab, two mAbs inhibiting the cytotoxic T-lymphocyte antigen-4 receptor, being occasionally seen with nivolumab, another immune checkpoint inhibitor. Enhanced antitumor immunity is the suggested mechanism of action of these drugs and autoimmunity the presumptive mechanism of their toxicity. Recently, ipilimumab has been licensed for the treatment of patients affected by metastatic melanoma. With the expanding use of these drugs, hypophysitis will be progressively encountered by oncologists and endocrinologists in clinical practice. The optimal management of this potentially life-threatening adverse event needs a rapid and timely diagnostic and therapeutic intervention. Hypopituitarism caused by these agents is rarely reversible, requiring prolonged or lifelong substitutive hormonal treatment. Further studies are needed to clarify several clinical and pathogenic aspects of this new form of secondary pituitary dysfunction.European Journal of Endocrinology 169 R153-R164

show abstract

Section: Introductionmentioning

confidence: 99%

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Torino

Barnabei

Paragliola

et al. 2013

European Journal of Endocrinology

108

103

View full text Add to dashboard Cite

show abstract

“…These manipulations disrupt cellular permeability barriers and potentially lead to alterations of drug concentrations thus impairing proper drug localization and correct quantification. Along with sensitive and spatial quantification techniques, bioassays and molecular biology methods are still mandatory when defining important molecular and cellular functions related to cellular drug exposure and action 16,17 . Combined with concentration measurements, they help in establishing cellular concentration–response relationships and guide therapies.…”

Section: Introductionmentioning

confidence: 99%

Approaching sites of action of drugs in clinical pharmacology: New analytical options and their challenges

Longuespée

Theile

Fresnais

et al. 2020

Brit J Clinical Pharma

View full text Add to dashboard Cite

Clinical pharmacology is an important discipline for drug development aiming to define pharmacokinetics (PK), pharmacodynamics (PD) and optimum exposure to drugs, i.e. the concentration-response relationship and its modulators. For this purpose, information on drug concentrations at the anatomical, cellular and molecular sites of action is particularly valuable. In pharmacological assays, the limited accessibility of target cells in readily available samples (i.e. blood) often hampers mass spectrometry-based monitoring of the absolute quantity of a compound and the determination of its molecular action at the cellular level. Recently, new sample collection methods have been developed for the specific capture of rare circulating cells, especially for the diagnosis of circulating tumour cells. In parallel, new advances and developments in mass spectrometric instrumentation now allow analyses to be scaled down to the cellular level. Together, these developments may permit the monitoring of minute drug quantities and show their effect at the cellular level. In turn, such PK/PD associations on a cellular level would not only enrich our pharmacological knowledge of a given compound but also expand the basis for PK/PD simulations. In this review, we describe novel concepts supporting clinical pharmacology at the anatomical, cellular and molecular sites of action, and highlight the new challenges in mass spectrometry-based monitoring. Moreover, we present methods to tackle these challenges and define future needs. K E Y W O R D S clinical pharmacology, mass spectrometry, personalized medicine, review, sites of action 1 | INTRODUCTION Clinical pharmacology studies the relevant parameters of drug fate (pharmacokinetics, PK) and efficacy (pharmacodynamics, PD) in humans in order to establish the dose-response and concentrationresponse relationship. It also defines intraindividual and interindividual modulators of these relationships, leading to different effectiveness, safety and dose requirements. Monitoring drug concentrations and effects is therefore of considerable importance during drug development, starting with the very first clinical trials. 1 Clinical pharmacology clarifies mechanisms of both beneficial and adverse drug effects in order to get closer to drug effectiveness monitoring. A drug's site of action can be defined at different scales: anatomical (the compartment the drug has to reach, e.g. tissues), cellular (the

show abstract

“…Monoclonal antibody (Mab), which is shown to bind to an epitope of some antigen, has received extensive attention in the research of tumor diagnosis and therapy applications [ 16 ]. In the present study, we focused on a new anti-CAIX monoclonal antibody, studying the specific optical imaging of CAIX in the mice bearing human HT-29 tumor xenografts using Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5).…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts

Bao

Liu

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research.

show abstract

Production, Novel Assay Development and Clinical Applications of Monoclonal Antibodies

Cited by 10 publications

References 64 publications

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

ENDOCRINE SIDE-EFFECTS OF ANTI-CANCER DRUGS: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses

Approaching sites of action of drugs in clinical pharmacology: New analytical options and their challenges

Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts

Contact Info

Product

Resources

About