Insights into Editorial: New approach to drug delivery combines biologics and antibody-drug conjugates

Context:

A type of nanoparticle designed by researchers from University of Massachusetts, Amherst, in the U.S., embodies a new approach to treating diseases that could potentially revolutionise the field.

This combines concepts of biologics and antibody–drug conjugates to produce protein–antibody conjugates that can be used for targeted drug delivery in the case of pancreatic cancer cells, for example.

The team has tested the mechanism in cell lines in the lab and now plans to move on to studying it in mouse models.

Biologics and antibody-drug conjugates:

1. A biologic drug (biologics) is a product that is produced from living organisms or contain components of living organisms. Biologic drugs include a wide variety of products derived from human, animal, or microorganisms by using biotechnology.
2. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances.
3. Biologics are used to target a defective protein in the system by delivering proteins to it.
   1. Example: If a person is short of insulin, which is a protein, they are given a shot of this to balance the system. This is referred to as insulin treatment.
4. Despite the usefulness of biologics, one drawback of this method is the inability of this method in taking protein specifically inside the affected cells. This mode of protein delivery to cells can be a breakthrough in medical field.

Antibody conjugates:

1. The other concept is of using antibodies for drug delivery.
2. Antibodies are something the body produces to detect a foreign substance inside the body.
3. We can develop antibodies to recognise anything that does not belong in our bodies.
4. That includes cancer cells as well. If there is something different on the surface of a cancer cell compared to a healthy cell, you can design the antibody that selectively goes to the cancer cell.
5. Drug molecules can be attached to the antibody, forming drug–antibody conjugates.

Monoclonal Antibodies:

1. Antibodies are proteins produced naturally by the immune system that target a specific foreign object (antigen).
2. They are called monoclonal Antibodies (mAbs) when they are produced by clones derived from a single parent cell.
3. They are man-made proteins that act like a human antibody in the immune system. They are made by cloning a unique white blood cell.
4. mAbs have monovalent affinity, it binds only to the same epitope i.e. the part of an antigen that is recognized by the antibody.
5. They are designed to perform many roles, like they can be used to carry drugs, toxins, or radioactive substances directly to affected cells.
6. mAbs are used to treat many diseases, including some types of cancer.

Two approaches to drug delivery:

1. The new concept, namely, Protein–Antibody Conjugates or PACs, combines two different approaches to drug delivery.
2. One is biologics, where the idea is to target a defective protein in the system by delivering proteins to it. An example of this is the case of insulin treatment.
3. If a person is short of insulin, which is a protein, they are given a shot of this protein which balances the system.
4. The reason this works is because we need a circulation of insulin outside the cells and not inside the cells.
5. Now, we have 20,000 proteins and when one of these is malfunctioning, we have no way of taking that protein specifically inside the cell. That is a big problem in biologics.

Undruggable cases: Pancreatic cancer is an example:

1. There are types that are considered undruggable. In 90% of pancreatic cancers, this is the case.
2. We know what we should target but we do not know how to design drugs that will bind. But with proteins we know we can design molecules that will bind to the target.
3. In a telling analogy, he compares the protein–antibody conjugate to an addressed envelope containing the drug.
4. The antibody plays the role of the address and indicates the cell where the drug should precisely be delivered.
5. The group also realises that biology involves complexity and that this method may well fail if it is not tuneable.
6. The researchers are planning to test this concept in mouse models as the next step.

Conclusion:

Prof Thayumanavan’s group developed protein–antibody conjugates or PACs, which have a protein attached to the antibody, and this conjugate can zero in on say, pancreatic cancer cells.

This could have an impact on incurable diseases. Most drugs work this way: If the protein has a particular shape bent concave like a cup for example, the drug is designed to fit into the bent portion, like a key into a lock, so that the protein’s function is inhibited, and it cannot function.

But some of the proteins have an open structure, it is difficult to design a drug that can bind to it, because it is so wide.

However, using a protein molecule, which is typically large, can solve this problem.

It will be a gamechanger if we can take the protein inside the cell. So, people have been looking at protein delivery for a while.