From cancer therapy to diagnostics: a new protein tool

AIBN’s Dr Fahimeh Farokhinejad has designed a new protein tool for diagnostic blood tests by re-engineering the bispecific antibody, typically used in cancer therapies.

“The exciting thing about proteins is that we can re-engineer them to design new functions to help in medicine and address real-world healthcare challenges” she said.

As part of Chris Howard’s research group, Dr Farokhinejad works with these powerful engineered proteins, bispecific antibodies, capable of binding two different targets at the same time. 

“Bispecific antibodies are amongst the most powerful and versatile protein tools that we have.”

“Our team uses bispecific antibodies for mRNA delivery in cancer therapy and vaccination so I began to ask whether we could also adapt them for diagnostics?”

What are bispecific antibodies?

“Antibodies by design only bind to one molecule, but our bispecific antibodies are designed with two arms that can bind two different molecules simultaneously,” said Dr Farokhinejad.

One arm recognises a biological target, while the other one interacts with components of nanoparticles, such as polyethylene glycol (PEG), which encapsulate a drug.

The biological target could be a receptor on cancer cells and the drug could be a cancer treatment.

Adapting for diagnostics

“The bispecific antibody can be specific for any disease you want to target.”

Dr Farokhinejad designed a bispecific antibody to detect cytokines, immune response molecules thought to be a biomarker in major depressive disorder.

The level of cytokines has been shown to fluctuate in the disorder and can give insights into the biology behind depression.

A sensitive tool

With one arm of the bispecific antibodies targeting cytokines and the other recognising PEG molecules on labelled nanoparticles, a sensitive detection system is generated for cytokines.

“We integrated the new protein tool with a sensitive immunoassay and monitored changes in the immune system in small quantities of blood,” Dr Farokhinejad said.

“In diagnostics, it's important for the tools to be very sensitive and precise and we are able to detect cytokines at the level of a single molecule.”

The right orientation

Attaching antibodies to nanoparticle surfaces has been a persistent challenge in this field.

Traditionally it has been achieved through chemical bonding, which has several drawbacks.

A limitation is that antibodies bind in random orientations, reducing sensitivity because not all the antigen-binding sites are optimally exposed.

“When we compared the bispecific method to chemical bonding, we saw a massive boost in detection of the target because of the correct orientation of the antibodies.”

The future

Now Dr Farokhinejad has demonstrated the robustness of this approach in patients with major depressive disorder, she is motivated to advance more diagnostics.

“Using these protein tools we can create highly sensitive diagnostic platforms spanning cancer to infectious diseases, with an emphasis on approaches that are precise, cost-effective, and time efficient.”

This research is published in Small Methods.

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