Immunotherapy Research

I've been doing a little more research on the exciting new research direction of harnessing the body's own immune system to fight cancer.  One of the most promising areas of research involves activating the body's T cells.  I'm going to try to give a layman's explanation of this, which I hope is not full of you know what.  Bear with me here.

electron microscope photo of T cell

T cells are a type of white blood cell that are the immune system's strike force against foreign invaders and diseased cells.  Antigens from the cancer cells are collected by antigen-presenting cells (APCs) and then transmitted to the T cells, along with a trigger protein, B7, which tells the T cells to attack.  The T cells are then sent on a search and destroy mission against the cancer cells.  T cells have a protein receptor, PD-1 (aptly named Programmed Death-1), which allows them to destroy cells that they contact.  In order to keep the T cells from destroying healthy cells, all healthy cells have a protein co-receptor, PD-L1.  When PD-1 is bound by PD-L1, this turns off or deactivates the T cell, thus saving the healthy cell.

The T cells also have another protection against destroying healthy cells. A receptor called CTLA-4 on the T cell itself can prevent B7 from doing its job in order to “keep the brakes on” the immune system.

Now I'm going to turn to literature.  I just recently read John LeCarre's famous spy novel, Tinker, Tailor, Soldier, Spy.  In it, the British spy, George Smiley, battles his Russian spy nemesis, Karla, who has planted a high-level mole in the British spy network, MI5.  In this story, Smiley tries desperately to uncover the secret mole who is undermining Britain's defenses.

Here, the cancer is Karla, and the cancer researchers trying to unravel this mystery to protect the immune system represent George Smiley trying to protect Britain.  The cancer, like Karla, is brilliant, resourceful, and difficult to beat.  The cancer mole managed to penetrate the immune system.  It has essentially stolen the PD-1/PD-L1 mechanism from normal cells in order to evade attack by the immune system!  However, as with Smiley, cancer researchers are ingenious, dogged, and determined.  They have recently discovered this mole in our cancer defenses and are now mounting a counter attack.

PD-1 inhibitors have been developed and are now in clinical trials.  The graphic below shows the mechanisms for breaking the bond between PD-1 and PD-L1, allowing the T cells to continue on their search and destroy mission.  Other antibodies are also in testing to inhibit the CTLA-4 receptor on the T cells, allowing them also to proceed to attack the cancer cells.
 

How PD-1 inhibitors activate T cells against cancer cells

There is an interesting discussion of these research approaches along with some of the ongoing clinical trials at this website:  https://www.smartpatients.com/pathways/pd-1.  Some of the monoclonal antibodies, such as Nivolumab and Ipulimumab, are showing promising results in clinical trials.  So far, the most dramatic results have been for melanoma, non-small cell lung cancer and kidney cancer, but these results should be encouraging for MM research as well.

One of the interesting things about immunotherapy is that the results seem to last longer than the therapy itself.  Once the T cells have been armed with the immunization, the results seem to be be very durable, even after the treatment has been discontinued.

I hope I haven't bored you or overwhelmed you with technical stuff.  But I like to have a picture of what is happening in MM research and I'm very encouraged by this approach.  I was happy to notice that Dana Farber has been on the forefront of this research.  Dr. Gordan Freeman of DFCI led the discovery of the PD-1 protein.

It's all good.