Immunity vs. Cancer: Beating blood cancers with CAR-T cells
Cancer Immunity CAR T

Immunity vs. Cancer: Beating blood cancers with CAR-T cells

Dr. Talia Henkle
Dr. Talia Henkle

In 10 seconds? Scientists have figured out how to use intricate cellular engineering to turn T-cells into enhanced cancer-killing machines–AKA CAR-T cells–that have been remarkably successful in treating multiple types of blood cancers.

What’s the story? In our Immunity vs. Cancer series so far, we’ve talked about how our killer T cells help attack cancer. This power has heartened scientists who are looking to enhance T cells’ killing abilities by developing new anticancer immunotherapies. It's not all that straightforward, though: T cells are intricately regulated (turned on and off) by our bodies, which keeps them from being the ideal cancer-killing weapons that researchers had hoped they would be.

Oh no! What’s stopping them from being superheroes?  Scientists realized that the success of anti-cancer T cell boosting therapies depended on whether an individual had generated anti-cancer T cells before receiving the therapy (a random process). Remember: each of your T cells has its own specificity (i.e. They have ONE job, be it going after either a virus, a bacteria, or a tumor), and is turned on when, and only when, it detects that exact target. On top of that, only 1 in 100,000 new T cells in our bodies is specific for any given target. All this to say–gassing up T cells with immunotherapies like immune checkpoint inhibitors is only helpful if an ‘inactive’ anti-cancer T cell army already exists in the first place. Of course, that begs the question: can we bypass the issue of whether there are anti-cancer T cells available and just engineer them to be more potent cancer-killing weapons?

Oh, I thought I was asking questions but yeah, can we? Welcome to the field of CAR-T cell (Chimeric Antigen Receptor-T cell) therapies! In this field, researchers take an individual’s T cells and, indeed, engineer them to become specific for cancer. Then they implant the cells back into the patient–negating the need for the patient to have developed their own anti-cancer T cell army.

That’s pretty cool! How do they do that? CAR-T cell engineering is a true testament to the importance of basic sciences (Think: cell biology, biophysics, chemistry, etc.) to human healthcare. The mechanics are complicated, and new generations of CAR-T therapies keep adding layers of complexity. In brief, researchers essentially embed the surface of an individual’s T cells with cancer-specific antibodies that will activate the T cells to kill when they connect with their target—the cancer.

Illustration how specific anti-cancer receptors are added to T cells to make CAR-T cells Source:

Can I get an example? Of course! The first CAR-T therapies were FDA-approved in 2017 to treat a cancer called Acute Lymphoblastic Leukemia (ALL)--which is made up of cancerous versions of immune cells called B cells. CAR-T treatment for ALL has had impressive success in patients who previously had no other treatment options–with generally 80% of patients showing improvement and 60% of which had complete responses (AKA no detectable tumors post-treatment)!

That’s amazing! Why so much success? ALL and other B cell cancers are the perfect targets for CAR-T therapies for multiple reasons. Firstly, B cells can easily be distinguished from other cells in the body by a single cell-surface protein–the ideal target for the CAR-T antibody receptor. Secondly, humans can survive without B cells (cancerous or not). This means CAR-T cells can kill non-cancerous B cells without lethal effects–something that is not the case for other tissues, say the brain or lungs. Thirdly, B cell cancers are gooey tumors in the bloodstream, meaning they are easily penetrable tumors right within the direct line of attack of newly implanted CAR-T cells.

Is there a catch? How’d you know? About 75% of B cell cancer patients experienced serious side effects, like neurotoxicity, to the first-generation CAR-T therapies. What's more, although CAR-T cells are designed to live in your body forever, a significant proportion of patients will relapse (their cancer will come back) after treatment, thanks to cancer’s sneaky resistance tricks like mutations. Another drawback of CAR-T therapies is that they have not been very successful against solid tumors, which represent the vast majority of existing cancers. Stay tuned for our next Immunity vs. Cancer digest to learn what scientists are doing to minimize the side effects of CAR-T cells and improve their functionality!

Life or debt decision

CAR-T cells have made the difference between life and death for some patients with no other options. With FDA approvals for multiple different CAR-T therapies, now more than 100 clinics around the US are administering these treatments and saving lives.

These highly technical treatments come with a hefty price tag between $300K-500K. That doesn’t even include the costs of other necessary drugs or hospital costs associated with side effects–which may bring the total cost upwards of $1million per patient.

Luckily, due to the significant quality of life increase, CAR-T treatment is covered under Medicare, but due to variable insurance coverage in the US, these treatments are far from accessible to everyone who may benefit.

Dr. Talia Henkle has distilled 3 research papers, saving your 10.5 hours of reading time

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

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