ADC Development: The Questions Running in the Background

You’ve had food stuck in your teeth at some point during a conversation you thought was going well. Or toilet paper trailing from the back of your shoe on a day you felt particularly put together. Maybe you’ve even forgotten to color in your very blonde eyebrows and spent the rest of the day looking like someone erased the top half of your face. But you had no idea. You’re walking around with the quiet, complete confidence of someone operating on incomplete information.

You weren’t wrong about anything you could see. You just couldn’t see everything, which is a different problem than getting a bad result. A bad result tells you something is wrong, but this doesn’t. This happens in the lab too. The number is clean, the program is advancing, and somewhere in the data, something is happening that your readout has no way to show you.

ADC development has a version of this problem. The cytotoxicity readout is real, reliable, and correct. It’s also an aggregate, and an aggregate compresses everything that happened into a single number. That number can’t tell you which mechanisms produced it, which ones are underperforming, or what to change if the program stops working. It just tells you cells died, or they didn’t. You’re walking around with the quiet, complete confidence of someone operating on incomplete information.

Cytotoxicity: Where Every Program Begins

Cell viability assays were built to answer one question: did the cells die? Increase the dose, more cells die. Decrease it, fewer do. The curve is clean, the data is reliable, and the payload is doing what it was designed to do. For cytotoxicity, it’s the right question to ask.

That question has an established platform with consistent, reproducible data: our CellTiter-Glo® and RealTime-Glo™ Assays.

For most ADC programs, this is where the measurement work starts and stops, but it should only be where it starts. The question they answer well is only one of several your ADC is raising. The number means what it says, but the question it answers has a boundary, and the boundary leaves you with an incomplete picture.

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Small Molecule Therapies and Immunotherapies: An Introduction to Targeted Cancer Treatments

Cancer is a deceptively singular term for hundreds of different diseases. These diseases can affect almost any part of the body.  In the United States, cancer is the second most common cause of death (1). At its most basic level, however, cancer is the abnormal and uncontrolled division of cells resulting from genetic changes in one or more cells.

This prolific cell division is what many standard chemotherapies act upon. These therapies are developed to kill rapidly dividing cells but often don’t discriminate between normal and cancerous cells. In contrast, targeted therapies are designed to interact with (or target) specific pathways, processes or proteins whose abnormal behavior is associated with cancer development and growth. Targeting these abnormal cellular functions can counteract cancer in different ways. They can interfere with tumor growth, carry other drugs into tumor cells or help the immune system find and kill cancerous cells. Targeted therapies can be loosely divided into two categories: small molecule therapies and immunotherapies.

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