Interested in learning about monoclonal antibodies (mABs), how they are made, and what they are used for in research, diagnosis, and therapy?
Smaller size packs a stronger punch – Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens
Very educative review on recent advances in small antibody fragments targeting tumor-associated carbohydrate antigens
Glycans represent the most versatile post-translational modification in nature and surround all human cells. Unique glycan structures are monitored by the immune system and differentiate self from non-self and healthy from malignant cells. Aberrant glycosylations, termed tumor-associated carbohydrate antigens (TACAs), are a hallmark of cancer and are correlated with all aspects of cancer biology. Therefore, TACAs represent attractive targets for monoclonal antibodies for cancer diagnosis and therapy. However, due to the thick and dense glycocalyx as well as the tumor micro-environment, conventional antibodies often suffer from restricted access and limited effectiveness in vivo. To overcome this issue, many small antibody fragments have come forth, showing similar affinity with better efficiency than their full-length counterparts. In this paper, small antibody fragments against specific glycans on tumour cells and highlighting their advantages over conventional antibodies are presented.
Sana Khan Khilji, Charlotte Op ‘t Hoog, David Warschkau, Felix Goerdeler, Anika Freitag, Peter Seeberger, Oren Moscovitz
Lilly’s Alzheimer’s drug donanemab slows cognitive decline by 35% in PhIII
An experimental Alzheimer’s drug developed by Eli Lilly and Company slowed cognitive decline by 35% in a late-stage trial, providing what experts say is the strongest evidence yet that removing sticky amyloid plaques from the brain benefits patients with the fatal disease.
Lilly’s drug, donanemab, met all goals of the trial: It slowed the progression of Alzheimer’s by 35% compared to a placebo in 1,182 people with an early-stage disease whose brains had deposits of two key Alzheimer’s proteins, beta-amyloid as well as intermediate levels of tau, a protein linked with disease progression and brain cell death.
See the article on reuters.com: Lilly drug slows Alzheimer’s by 35%, bolstering treatment approach
Method for Reduced Aggregate Formation in Downstream Processing of Bispecific Antigen-Binding Molecules
This is a great example of using CDs in a downstream processing method to produce bispecific antigen-binding molecule. In Amgen‘s invention, β-CD is applied in the process either in a buffer applied in the filtration step or added to the filtration pool after the UF/DF filtration step to keep the product in a non-aggregated form.
Yan Wang; Nicholas Marchand; Robert Brake; Maria Perry; Ashish Sharma; Eugene Sun
Incorporation of Hydrophilic Macrocycles Into Drug-Linker Reagents Produces Antibody-Drug Conjugates With Enhanced in vivo Performance
Antibody-drug conjugates (ADCs) have begun to fulfill their promise as targeted cancer therapeutics with ten clinical approvals to date. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers. In this paper from Abzena, the effect of incorporating hydrophilic macrocycles like cyclodextrin into reagent structures on the in vitro and in vivo behavior of ADCs.
Nick Evans, Ruslan Grygorash, Nicolas Camper, Mark Frigerio, Matthew Bird et al
An interesting application is highlighted in the patent of RemeGen荣昌生物: methyl-BCD is used in antibody-drug conjugate formulations where the primary benefit is that ADC dose can be lowered (due to higher efficacy), which leads to mitigating safety concerns lowering costs, and patient treatment costs. Fascinating, huh? (Figure: Araris Biotech AG)
Have you ever tried using cyclodextrin to prevent protein folding and to stabilize them with such safe excipients instead surface active agents? From the patent of Tamas Sohajda, our board member, you can learn more about this potential.