Mass Spectral Analyses of Labile DOTA-NHS and Heterogeneity Determination of DOTA or DM1 Conjugated Anti-PSMA Antibody for Prostate Cancer Therapy

Toxicological Protein Biomarker Analysis—An Investigative One-week Single Dose Intravenous Infusion Toxicity and Toxicokinetic Study in Cynomolgus Monkeys using an Antibody–cytotoxic Conjugate against Ovarian Cancer

“…Therefore, it measured the total concentration of antibody with at least one cytotoxin conjugated to MLN8866. The MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry) was used to identify levels of cytotoxic (CT) conjugation in CT-antibody conjugate (4).…”

“…The success of an ADC to specifically deliver a cytotoxin to a cancer cell depends on many factors, including the tissue distribution of the epitope against which the antibody is targeted and the stability of the linkage between the cytotoxin and antibody. The number of ADCs in development has rapidly increased over the past several years (1)(2)(3)(4)(5)(6)(7). However, only one ADC (Gemtuzumab Ozogamicin for acute myeloid leukemia) has been approved to date by the US FDA (8,9).…”

Charge-based analysis of antibodies with engineered cysteines

“…1,2 Within this product class, antibody-drug conjugates (ADCs) are attracting significant recent attention. [3][4][5][6][7][8][9][10][11][12][13] ADCs may improve the therapeutic index of cytotoxic drugs by using the interaction of the antibody with tumor-specific antigens to deliver chemotherapy directly to cancer cells, thereby reducing toxicity to normal tissue. THIOMABs are antibodies with an engineered and unpaired cysteine residue on each heavy chain in a non-CDR region.…”

“…13 These can be used as intermediates to generate ADCs. Unlike conventional antibody conjugation strategies, where drug attachment is either through exposed lysine residues 5,6 or through inter-chain disulfides [7][8][9] forming a heterogeneous mixture of ADCs with different drugto-antibody ratios (DARs), the THIOMAB platform provides one specific site on each heavy chain (Fab region) for drug attachment. Therefore, conjugation of a THIOMAB generates a more homogenous ADC product with a primary DAR close to two.…”

A Novel Engineered Anti-CD20 Tracer Enables Early Time PET Imaging in a Humanized Transgenic Mouse Model of B-cell Non-Hodgkins Lymphoma

“…DOTA-FN3 was purified by HPLC and lyophilized for 64 Cu labeling. The number of DOTA chelators conjugated to each FN3 molecule was calculated by mass spectrometry by comparing the mass of FN3 and Do-FN3 (31,32).…”