As an emerging class of biologics, bioconjugates
show great potential to not only improve existing therapeutics, but to create
entirely new methods of treatment as well.
Anitbody Drug Conjugates (ADCs) are an important subset of these
bioconjugate compounds but they do, however, come with a series of limitations. Catalent
recently published a whitepaper
outlining some of the ways to overcome these shortcomings. One of the authors of this study, David
Rabuka, PhD, was able to further break down the restrictions of current ADC
technology as well as provide us with some added insight on SMARTag technology.
What’s the biggest implication you see of SMARTag
technology?
I really like the idea of control over molecular architecture. Approaching bioconjugation in a controlled and
thoughtful process. An analogy I like that I have heard more and more is
a structure activity relationship (SAR) approach to generating bioconjugates.
What would be the benefit
of this SAR approach to generating bioconjugates?
When
doing medicinal chemistry on a small molecule for example, one approaches
optimizing the compound by making systematic chemical changes to the molecule
to see how those slight changes affect the biological properties of the
potential drug. Having an approach or a technology that allows one to do
this in the context of bioconjugation has until recently not been possible.
Now it is (using technologies such as the SMARTag) and it opens up
possibilities for optimization and understanding of ADCs that were previously
inaccessible.
You talk about some of the limitations of current
ADC technologies. How close are those to being addressed?
I think a number of the issues are being rapidly addressed while a
few of the limitations are still a little behind. I think the concept of
site-specificity and dealing with heterogeneous mixtures is playing out in a
number of different groups with one compound already in the clinic. I
think linker design and some of the more chemical elements (including new
payloads) of an ADC are not as far along.
What’s one thing readers of this paper should take
away?
That novel approaches to bioconjugate generation can provide
simple paths to optimized biotherapeutics and next generation ADCs.
You can download the full whitepaper
from Catalent here.
Want more on the latest in bioconjugate research?
Check out Bioconjugates: From Targets to
Therapeutics, June 4-6, San Francisco, CA. You can download the brochure here.
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