ABSTRACT
Introduction: Antibody-Drug Conjugates (ADCs) are becoming increasingly important weapons in the fight against cancer, as evidenced by the growing number of approved products. The complex nature of an ADC means that there is a vast array of choices to consider in the design of such drugs.Areas covered: We provide an overview of developments in each facet of ADC structure: the antibody, linker, and payload. Looking at the current clinical landscape, we discuss trends that have led to the evolution of ADC design.Expert opinion:Following a history of setbacks and high discontinuation rates, the understanding of the ADC field has grown. If developers can obtain a firm grasp of the structure-function relationship of their molecule, we expect the advances in ADC design to translate to improved clinical success. Moreover, the breadth of ADC applications will continue to expand to target new indications with novel targets and payloads.
Subject(s)
Immunoconjugates , Neoplasms , Antibodies , Humans , Immunoconjugates/therapeutic use , Neoplasms/drug therapyABSTRACT
Cell therapies and tissue-engineered products that contain living cells are potentially some of the most exciting of the novel therapeutic products currently under development. These products, however, present a number of important safety issues, particularly with respect to the transmission of human viruses. In addition, the short shelf life of these products precludes the normally extensive characterization performed on other biotherapeutic products. Careful examination of the risks and extensive testing of the raw materials have been used in place of product testing to ensure safety.
Subject(s)
Cell- and Tissue-Based Therapy/standards , Consumer Product Safety/legislation & jurisprudence , Disease Transmission, Infectious/prevention & control , Product Surveillance, Postmarketing/standards , Risk Assessment/methods , Risk Assessment/standards , Tissue Engineering/legislation & jurisprudence , Cell- and Tissue-Based Therapy/methods , Consumer Product Safety/standards , Disease Transmission, Infectious/legislation & jurisprudence , Humans , Microbiological Techniques/methods , Microbiological Techniques/standards , Product Surveillance, Postmarketing/methods , Quality Assurance, Health Care/legislation & jurisprudence , Quality Assurance, Health Care/methods , Quality Assurance, Health Care/standards , Risk Assessment/legislation & jurisprudence , Skin, Artificial/standards , Skin, Artificial/virology , Tissue Engineering/methods , Tissue Engineering/standards , United StatesABSTRACT
Bovine polyomavirus (BPyV) is a member of the Polyomaviridae, a virus that was originally thought to be of simian origin but was later shown to be of bovine origin, the primate cultures having been contaminated through the use of foetal bovine serum. The significance of this agent to the biotechnology industry cannot be underestimated. The presence of BPyV in serum batches poses a serious risk for the contamination of human therapeutic products. The current PCR based assays provide a means of detecting virus sequences but give no indication as to the infectious nature of the virus. The communication reports the successful development of an assay to detect infectious BPyV using an in vitro amplification system followed by PCR. A lengthy culture period on bovine cells was required before replicating BPyV could be detected and distinguished from non-replicating virus in the cell culture supernatant. A mock-test assay using foetal bovine serum positive for BPyV showed that there was no evidence of replicating BPyV in the serum sample. The BPyV spiked serum control showed that replicating virus was present thus confirming that the serum itself did not inhibit replication of the virus. Cells harvested during the culture period were subjected to fixation, embedding and sectioning and examined by electron microscopy. Intact virus-like particles of approximately 40-50nm were observed in the nucleus of the bovine kidney cells, the site of polyomavirus replication.
