A BiTE idea: engineered antibodies to attack tumors
Cancer Cancer therapy BiTE

A BiTE idea: engineered antibodies to attack tumors

Dr. Talia Henkle
Dr. Talia Henkle

In 10 seconds? Bi-specific T cell engagers (BiTEs) are an emerging cancer treatment strategy that work both to activate anti-cancer T cells and pull them in to kill tumors.

Wow, that sounds high-tech! And it is. BiTEs are essentially super mutant antibodies. We’ve talked a lot about other types of antibody-based cancer treatments like immune checkpoint therapies, but BiTEs take the engineering to the next level.

OK, I know that immune cells can be unleashed on tumors but antibodies?? Yes, they can! Quickly, some background. Antibodies are naturally produced by our immune system to protect us against foreign invaders (pathogens). They do this by attaching to (binding) specific elements on pathogens and signaling the immune system to handle the threat. The key feature here—binding to one specific target.

And why is this feature important? Well, scientists have figured out how to develop their own antibodies for a wide range of therapeutic and scientific purposes. Therapies like immune checkpoint inhibitors are antibodies that are developed to bind to immune cells called T cells and activate them to kill cancer. However, this strategy hinges on the probability that once re-activated, the cancer killing T cells will travel to the tumor and kill it. And in this case, probability frequently doesn’t work in patients’ favor.

OK, thanks for the background but what about BiTEs? Scientists asked the question of whether they could design a molecule that could encourage activated T cells (immune cells) to connect with the tumor more easily. Thus, the creation of BiTEs, which are engineered molecules that utilize features of antibodies to recognize two distinct targets—one that activates T cells and the other that binds to the tumor.

And why is that important? This way, cancer-killing T cells can be simultaneously activated and drawn towards the tumor to increase the probability that these T cells both travel to the tumor and kill it.

BiTEs can activate T cells and bring them to tumor cells to promote cancer-cell killing. Source:  Tian Z, et al. J Hematol Oncol (2021) 14:7

That sounds great in theory. But does it work in practice?  Similar to other emerging cancer therapies, like CAR-T cells, the greatest success has been seen in blood cancers. Multiple different BiTE therapies have been successful in treating different types of B cell (another type of immune cell) cancers.  One of the most successful treatments, blinatumomab, eliminated tumors in about 40% of patients in multiple clinical trials and is now FDA-approved to treat various types of B cell cancers.

That’s exciting! Yes, but it’s not perfect. Clearly, many of these patients (~60%) fail to fully benefit from BiTE treatment, and patients can experience dangerous side effects from the potent T cell activation (namely something called cytokine release syndrome which can be life-threatening).

So what’s next? For established treatments like blinatumomab, researchers are looking to combine BiTE treatment with other therapies like immune checkpoint therapy or chemotherapy (which has already seen some promising results). Combining treatments, AKA combination therapy, appears to be key for tackling many cancers! Otherwise, many other BiTE therapies are in the pipeline that are testing out innovative formulations and novel tumor targets.

How do antibodies work?

Antibodies are expertly designed by nature. You can imagine antibodies being shaped like the letter ‘Y’. In nature, the ‘V-shaped end (AKA Fab fragment) of antibodies will bind to pathogens, and then certain immune cells bind to the ‘stick’ end of the antibody (AKA Fc region).

If the Fab end binds a pathogen (i.e. a virus or bacteria) that is swimming around outside our cells, immune cells called macrophages latch onto the Fc end and will gobble up and kill the pathogen directly. This mechanism is how vaccines, which promote the formation of antibodies, work to prevent infection.

If the Fab end binds a pathogen that is too big for a macrophage to engulf (like a parasite), immune cells called Natural Killer cells will bind the Fc end and use the antibody as an anchor to latch on and inject toxins to kill it–a process called antibody-dependent cellular cytotoxicity or ADCC. ADCC is an important mechanism by which certain antibody-based treatments can help kill cancer cells.

Dr. Talia Henkle has distilled 2 research papers, saving your 7 hours of reading time

The Science Integrity Check of this 3-min Science Digest was performed by Dr. Jacquelyn Bedsaul.

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