Co-crystallisation and humanisation of an anti-HER2 single-domain antibody as a theranostic tool.

Human epidermal growth factor receptor-2 (HER2) is a well-recognised biomarker associated with 25% of breast cancers. In most cases, early detection and/or treatment correlates with an increased chance of survival. This study, has identified and characterised a highly specific anti-HER2 single-domain antibody (sdAb), NM-02, as a potential theranostic tool.

[Tc]-labelled anti-Programmed Death-Ligand 1 single-domain antibody SPECT/CT: a novel imaging biomarker for myocardial PD-L1 expression.

Background: Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 expression using [Tc]-labelled anti-PD-L1 single-domain antibody (NM-01) SPECT/CT.

Preclinical development and characterisation of Tc-NM-01 for SPECT/CT imaging of human PD-L1.

The level of expression of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) is a predictive biomarker for cancer immunotherapy, however, its detection remains challenging due to tumour heterogeneity and the influence from the binding of therapeutic agents. We recently developed [Tc]-NM-01 as a companion diagnostic imaging agent for non-invasive molecular imaging of PD-L1 by single-photon emission computed tomography (SPECT). The aim of the study was to evaluate the [Tc] radiolabelling of GMP graded NM-01 and its pharmacology, pharmacokinetics and toxicology.

Theranostic Approach in Breast Cancer: A Treasured Tailor for Future Oncology.

Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades.

HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging.

Purpose: The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development.

Results: Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients.

Early Phase I Study of a Tc-Labeled Anti-Programmed Death Ligand-1 (PD-L1) Single-Domain Antibody in SPECT/CT Assessment of PD-L1 Expression in Non-Small Cell Lung Cancer.

Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies demonstrates improvements in treatment of advanced non-small cell lung cancer. Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single-domain antibody, NM-01, against PD-L1, radiolabeled site-specifically with Tc for SPECT imaging, we aimed to assess the safety, radiation dosimetry, and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results.

Purified anti-CD3 × anti-HER2 bispecific antibody potentiates cytokine-induced killer cells of poor spontaneous cytotoxicity against breast cancer cells.

Background: Chemical crosslinking is the most straightforward method to produce bispecific antibodies (BsAb) for arming ex vivo activated cytotoxic T lymphocytes. However, heterogeneous polymers are produced by chemical crosslinking. Currently, it is not known under what circumstances or to what extent further purification is needed.

Molecular identity of a pan cancer marker, CA215.

The molecular nature of cancer-associated antigen, CA215 which reacts with RP215 monoclonal antibody and its unique epitope(s)was characterized. RP215 was initially selected and produced from one of 3,000 hybridomas which were generated from mice immunized with the cell extract of OC-3-VGH ovarian cancer cells. This cancer-associated antigen from various sources including cancer cell extract, shed culture medium and affinity-purified forms was analyzed by MALDI-TOF MS (Matrix Adsorption Laser Desorption Ionization-Time of Flight Mass Spectrometry), Western blot, carbohydrate profiling as well as enzyme immunoassays.

Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody.

RP215 monoclonal antibody was originally generated against OC-3-VGH ovarian cancer cells. It was shown to recognize specifically a carbohydrate-associated epitope(s) of cancer cell-expressed immunoglobulin heavy chains designated as CA215. Previous studies suggest that CA215 is expressed by all human cancer cell lines and tissues in both membrane bound and secreted forms.