Team:Korea HS/Human Practices

KOREA_HS

Designing a Hyperstable Antibody with
Cell-penetrating Peptide for Intracellular Targeting

Human Practices

Human Practices

Interview 1

Dr. Taegwon Oh

Director of R&D, Cellid Co., Ltd

We discussed a problem our team faced during our lab procedures in our first interview. The HRas G12V did not send the expected western blot signal that would confirm our protein is correct. He suggested many possible reasons for this problem, such as a low protein concentration, incomplete transfer to the membrane, unattached primary antibody, or interference in detecting the signal. These were considered possible causes of unclear results; however, he said it is hard to define what specific reason led to a failure. Therefore, Dr. Oh advised us to send the transferred membrane to another company to get the sequence checked. He also informed us that it is okay not to develop a perfect plan but to keep an open mind about the results. This interview was beneficial in engineering because, due to his advice, we verified that it was our protein after membrane sequencing. The project became more cost-effective and time-efficient.

Interview 2

Mr. Ho-juhn Song

Founding Member of GENOSCO and CEO at Pinetree Therapeutics

The central theme of our second interview was the limitations and advantages of our therapy. We asked Mr. Song if our therapy would be effective against cancer cells and other diseases that we can target. He responded that Ras targeting has the potential to develop into a drug. He also stated that our idea for cell-penetrating medicines is valid and could potentially have a wide application, including tumors.

He informed us that antibodies have a high affinity and high specificity for antibody treatments and should be effective as antagonists - blocking and neutralizing. Some diseases that can be treated by antibodies are tumors, which have targetable proteins and an indicator, infectious diseases, and autoimmune diseases. He gave examples of existing approved treatments such as Septocima and Remicade. He said that compared to chemotherapy, which has severe side effects, antibody therapy works selectively and can differentiate healthy cells from cancerous ones; it therefore has fewer side effects and stays in the system for longer. However, antibodies may bind to healthy cells as cancer proteins aren’t 100% foreign. It can also be challenging to mass produce because it has to be specific to work on different patients.

He also advised that people usually start with small molecule solutions for intracellular targets, as there is no guarantee that antibodies can deliver. But the Ras has a structure that makes it very difficult for small molecules to target. Most small molecules target enzymes or receptors that the small molecules can bind to, but the Ras has many forms, making it hard for small molecules to inhibit it. There have been doubts as to whether it is possible to develop a small molecule drug targeting Ras. However, if there is a way to safely deliver antibodies to intracellular targets, I think it’s definitely worth researching.

Interview 3

Mr. Kim Min Soo

Research team leader of Orum Therapeutics

Our third meeting was focused on the real-life implications of our therapy. We asked if our therapy had a chance to be implemented in real life, what challenges developing this treatment would ensue, and the population affected by this therapy. He said that profit is a critical factor in deciding the development of drugs. When pharmaceutical companies see shaky or unreliable results, they may wish to shift their focus. They are very likely not to manufacture drugs that don't bring profit to them. Therefore, it is crucial for drugs to be desired by many people and cost-efficient.

We also discussed our project's advantages and improvements that need to be made. First, he told us that it could establish a new form of treatment because the intracellular targeting method is not used in current cancer therapeutics. He told us that it would be an innovative way to cure cancer if we keep building on it. However, there were also disadvantages of intracellular targeting. The cell-penetrating peptide attached can be dangerous, so it should be proven safe. Also, he suggested that we do not know any other side effects since it is not used in current therapeutics. We learned that our biggest challenge to face is to prove our antibody's safety and stability.