Cancer and the immune system – illustrated! (Part 3: T cell transfer therapies)

In Part 1 and Part 2, we overviewed the natural immune response to cancer, monoclonal antibody therapies, and cancer treatment vaccines. This time we’re talking about taking out a patient’s own anti-tumor cells, equipping them for a good fight, and putting them back in! We call these T cell transfer therapies.

One historical approach has been to isolate a patient’s own anti-tumor T cells that have infiltrated a tumor, culture them in a petri dish to re-awaken them and pump them up (since cancer cells tend to suppress healthy T cells that are trying to fight them).

A more recent approach has been to take out a patient’s T cells (irrespective of whether they specifically recognize the cancer cells), and to genetically engineer them to recognize cancer cells. These cells are then put back into the patient, and they are now programmed to get all fired up when they see their target. How does this work?

Introducing, the “CAR” T cell (“chimeric antigen receptor”):


This guy looks a lot like the T cell from earlier posts – except with one addition. Using viruses in the lab, scientists integrated new code into the T cells’ genome. This new code contains a fragment of an antibody that recognizes a target known to be on a cancer cell. The most recent generations of CAR T cells also include signal enhancers on the inside of the cell, so that when the antibody fragment on the outside finds its target, the signal is amplified quite a bit on the side of the cell, telling it to strongly attack the target cell and to signal for other cells to come help.


Wait, what? Did you just say an antibody fragment on a T cell? Yes, indeed! Scientists have made a bit of a B cell-T cell hybrid here. They’re using other components of the immune system to beef up the T cells. Pretty cool! You’ll also note that the T cell isn’t using its normal receptor (the TCR) to scan the cancer cells hands (MHC receptor). It’s using an entirely different mechanism that was engineered in.

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CAR T cell therapy┬átherapy has been pretty successful in treating, for example, cancers of B cell origin, by targeting a protein found on all B cells. Following from this, though, both healthy and cancerous B cells are destroyed. This turns out to be ok, as we’ve learned from years of experience with rituximab in B cell lymphoma and lupus; the immune system has enough redundancy that patients survive pretty well without their B cells (though are a bit more susceptible to infections).

When scientists began to try this therapy on other cancer types, they continued targeting proteins that were found both on healthy cells and on cancerous cells, usually with the target in greater abundance on the cancerous cells. At first, this proved problematic for healthy cells that were more critical for patient survival (such as lung cells). Scientists have since learned that they should select for lower affinity (weaker binding) CAR T cells because these cells will still recognize the cancer cell target, which has the target in high abundance, and the weaker affinity means that they’re less likely to bind to the healthy cells that express the target at lower levels.

This approach comes with a little more overhead than monoclonal antibody or treatment vaccine approaches because it requires extracting a patient’s own cells, manipulating them, and putting them back into the patient – so it’s not quite as “drug-like” as those other methods. However, it has shown some very promising results and is well worth the extra effort.

Learn more at the AACR and the CHOP.

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