生物分析および生物医学ジャーナル

In the journey of drug development through regulatory approval, product quality attributes of a biosimilar protein must compare within defined limits to those of the innovator product. Unlike small molecule drugs, whose structure can usually be completely defined and entirely reproduced, biologicals are typically more complex and consist of heterogeneous populations not entirely identical to an innovator product. Therefore, biosimilarity is generally demonstrated as having matched product quality attributes, comparable in vitro biological activity, and no clinically meaningful differences between the biosimilar drug and innovator product. The complexity of recombinant protein manufacturing processes, including expression systems (i.e., host cell line, expression vector, cell line development process), cell culture process conditions and related nutrient systems, such as cell culture media and feeds, present significant challenges to achieve the required product quality for biosimilars. To address these challenges, a systematic approach combining media toolbox methodology and bioprocess “knowhow” has been developed to screen and optimize manufacturing conditions that promote the desired product quality profiles of recombinant proteins. Results using this strategy are presented to highlight the efficacy of this approach and successful implementation in manufacture of biosimilar recombinant monoclonal antibodies.

Cancer is a heterogeneous group of diseases where abnormal cell growth with potential to invade other body parts takes control of normal homeostasis and becomes fatal if not timely and rightly treated. There are more than 100 types of cancers characterized so far and many yet to be identified. World Health Organization estimates, that worldwide in 2012 there were 4 million new cancer cases and 8.2 million cancer related deaths. Amongst various treatment options available for cancer, immunotherapy offers an approach where the focus is on enhancing or even inducing an antitumor immune response. Induction or enhancement of anti-tumor immune response is a formidable challenge in cancer because tumor cells use multiple immune evasion strategies and avoid being detected or eliminated by immune cells. Immune checkpoints refer to a network of stimulatory or inhibitory signaling pathways in the immune system which are critical in maintaining self-tolerance, limiting tissue damage and modulating the quality of immune response. Substantial evidence indicates that up regulation of inhibitory signaling molecules (CTLA - 4, PD - 1) by tumor cells subvert activation of tumor antigen specific Teffector cells. Therefore, blockade of inhibitory signaling pathways may be one potential way of revitalizing an exhausted immune response in tumors. Using this approach, antibodies directed against CTLA - 4 and PD - 1 have been shown an acceptable therapeutic benefit in preclinical models and cancer patients. This review will discuss the important immune checkpoints that have been identified critical to suppress anti-tumor immunity and have been exploited as drug targets.