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There is emerging, intense interest in antibody combination therapies. However, antibody combination therapies pose unique intellectual property challenges. In some instances, it may be difficult to obtain patents with claims that provide innovators with adequate protection for such inventions. Patent examiners often regard claims to a composition or use of an antibody in combination with another therapeutic agent as obvious if the individual components of the combination were both known and well-studied in the field for use in treating similar indications. Nevertheless, even if the individual components of a combination were known and generally effective, the combination therapy may not be obvious if there would not have been a motivation to specifically combine the individual components or if there was no reasonable expectation of success in combining the components. Antibody combination therapies may also offer fertile grounds for demonstrating objective evidence of nonobviousness for a particular combination, such as through unexpected results, if a sufficient nexus can be established across the scope of the claims and if the superior results constitute a significant improvement.The pharmacokinetic-pharmacodynamic relationship is extremely complex and tumour drug penetration is one key parameter influencing therapeutic efficacy. In the context of antibody-drug conjugates (ADCs), which has undergone many innovation cycles and witnessed many failures, this feature is being addressed by a number of alternative technologies. Immunoglobulin-based ADCs continue to dominate the industrial landscape, but smaller formats offer the promise of more-effective cytotoxic payload delivery to solid tumours, with a higher therapeutic window afforded by the more rapid clearance. Selpercatinib To make these smaller formats viable as delivery vehicles, a number of strategies are being employed, which will be reviewed here. These include identifying the most-appropriate size to generate the larger therapeutic window, increasing the amount of functional, cytotoxic payload delivered through conjugation or half-life extending technologies or other ways of extending the dosing without inducing toxicity.
Strategies to reinvigorate exhausted T cells have achieved great efficacy in certain subpopulations of tumor patients. Blocking the antibodies that target programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 induces durable responses in Hodgkin's lymphoma, melanoma, renal and lung cancers. T cell immunoglobulin mucin-3 (TIM-3) is another well-defined inhibitory receptor that is expressed in terminally differentiated Th1/Tc1 cells, which produces interferon gamma and cytotoxic molecules. It is also significantly expressed on forkhead box P3+ regulatory T cells and innate immune cells such as dendritic cells and macrophages.
By immunizing BALB/c mice with recombinant TIM-3 and screening of 20000 hybridoma clones, we selected a monoclonal TIM-3-blocking antibody (IBI104), which shows great efficacy
and
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IBI104 blocks phosphatidylserine interaction with TIM-3 but does not interfere with the interaction of TIM-3 with galectin-9 in ELISA assays. However,
administration of IBI104 induces the potent internalization of TIM-3 in activated T cells to the extent that it will shut down the entire TIM-3 mediated signaling regardless of the ligands. IBI104 shows potent anti-tumor efficacy when combined with anti-PD1
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Our results suggest that IBI104 is a promising blocking antibody for TIM-3-mediated suppressive signaling and can serve as effective cancer immunotherapy, especially in combination with anti-PD1.
Our results suggest that IBI104 is a promising blocking antibody for TIM-3-mediated suppressive signaling and can serve as effective cancer immunotherapy, especially in combination with anti-PD1.The use of augmented reality (AR) in providing three-dimensional (3D) visual support and image depth have been applied in education, tourism, historical studies, and medical training. In research and development, there has been a slow but growing use of AR tools in chemical and drug discovery, but little has been implemented for whole 3D antibody structures (IgE, IgM, IgA, IgG, and IgD) and in communicating their interactions with the antigens or receptors in publications. Given that antibody interactions can vary significantly between different monoclonal antibodies, a convenient and easy to use 3D visualization can convey structural mechanisms clearer to readers, especially in how residues may interact with one another. While this was previously constrained to the use of stereo images on printed material or molecular visualization software on the computer, the revolution of smartphone and phablets now allows visualization of whole molecular structures on-the-go, allowing rotations, zooming in and out, and even animations without complex devices or the training of visual prowess. While not yet as versatile as molecular visualization software on the computer, such technology is an improvement from stereo-images and bridges the gap with molecular visualization tools. In this report, we discuss the use of AR and how they can be employed in the holistic view of antibodies and the future of the technology for better scientific communication.A bispecific antibody (bsAb) can simultaneously bind two different epitopes or antigens, allowing for multiple mechanistic functions with synergistic effects. BsAbs have attracted significant scientific attentions and efforts towards their development as drugs for cancers. There are 21 bsAbs currently undergoing clinical trials in China. Here, we review their platform technologies, expression and production, and biological activities and bioassay of these bsAbs, and summarize their structural formats and mechanisms of actions. T-cell redirection and checkpoint inhibition are two main mechanisms of the bsAbs that we discuss in detail. Furthermore, we provide our perspective on the future of bsAb development in China, including CD3-bsAbs for solid tumors and related cytokine release syndromes, expression and chemistry, manufacturing and controls, clinical development, and immunogenicity.
