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Antibody Drug Conjugates (ADCs) are an emerging class of biopharmaceutical products for oncology, with the cytotoxic Pyrrol-oBenzoDiazepine (PBD) family of 'warheads' well established in the clinic. While PBDs offer high potency, they are also characterized by their hydrophobicity which can make formulation of the ADC challenging. Several approaches have been investigated to improve the physico-chemical properties of PBD-containing ADCs and herein a supramolecular approach was explored using cucurbituril (CB). The ability of CB to simultaneously encapsulate two guests was exploited to incorporate a 12-mer poly-ethylene glycol harboring a methyl-viologen moiety at one terminus (MV-PEG12), together with a PBD harboring an indole moiety at the C'2 position (SG3811). This formulation approach successfully introduced a hydrophilic PEG to mask the hydrophobicity of SG3811, improving the physical stability of the ADC while avoiding any loss of potency related to chemical modification.
This article was published in the following journal.
Name: Bioconjugate chemistry
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Semisynthetic vaccines consisting of polysaccharide antigens from microorganisms attached to protein carrier molecules. The carrier protein is recognized by macrophages and T-cells thus enhancing immunity. Conjugate vaccines induce antibody formation in people not responsive to polysaccharide alone, induce higher levels of antibody, and show a booster response on repeated injection.
The chemical and physical integrity of a pharmaceutical product.
An integration host factor that was originally identified as a bacterial protein required for the integration of bacteriophage Q beta (ALLOLEVIVIRUS). Its cellular function may be to regulate mRNA stability and processing in that it binds tightly to poly(A) RNA and interferes with ribosome binding.
Prosthesis, usually heart valve, composed of biological material and whose durability depends upon the stability of the material after pretreatment, rather than regeneration by host cell ingrowth. Durability is achieved 1, mechanically by the interposition of a cloth, usually polytetrafluoroethylene, between the host and the graft, and 2, chemically by stabilization of the tissue by intermolecular linking, usually with glutaraldehyde, after removal of antigenic components, or the use of reconstituted and restructured biopolymers.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...