RE:RE:To better understand the complexity of ADCs The empirical evidence is more biotech choose the ADC route over PDC, more ADCs have been approved than PDCs. There are potential pros and cons to both approaches but there are really no fixed rule. Each approach, each molecule tested, needs to be supported by it's own empirical evidence. There is only so much you can learn from these generalized statements. Docetaxel failed in pancreatic cancer according to Christian. Do you think docetaxel penetrates tumours worse than Th-1902? Did docetaxel fail for penetration reasons?
jfm1330 wrote: Back to serious stuff. I am now reading a good article on PDCs. I have not yet finished to read it, but this part is interesting, since again, they compare PDCs to ADCs:
Although these conjugates reached the market and proved the feasibility of this approach, antibodies have serious limitations. Most mAbs do not penetrate into tumors. With a molecular weight of about 150 kDa, they are too big to diffuse efficiently into malignant tissue (Dreher et al., 2006; Jain and Stylianopoulos, 2010). Monoclonal antibodies can be immunogenic, even when they have been humanized and they tend to aggregate in excretory organs like liver and kidneys (Borsi et al., 2002; van Schouwenburg et al., 2010; Carrasco-Triguero et al., 2013). Moreover, the generation of mAbs is very expensive as well as time-consuming and non-selective payload conjugation can lead to reduced product homogeneity (Nejadmoghaddam et al., 2019).
Most of these drawbacks can be eliminated by using smaller biomolecules like peptides.
jfm1330 wrote: Really great article. ADCs are a much more complex matter than I thought and more complexity means more possibilities for something to go wrong. It is quite technical, some understanding of biochemistry is necessary to understand the essence of what is explained in there. After reading that I am more convinced that a good peptide drug conjugate can be better than ADC, but it need to be good, good peptide, good linker and good target. That being said, ADCs and PDCs faced some shared challenges an that make this read interesting to identify and understand some of the potential problems that could be encountered by Thera's PDC. It is not a slam dunk at all.
https://ascopubs.org/doi/10.1200/EDBK_281103