How Mice Help Cure Leukemia

By Shlomo Maital   

CAR-T Mouse

 Writing in the Philadelphia Inquirer, reporter Sarah Gantz informs us:

     “The first two recipients of a groundbreaking cancer treatment developed at the University of Pennsylvania remained cancer-free a decade later, leading researchers to utter a word that’s typically taboo in cancer circles: cure.   Penn researchers in 2010 treated their first chronic lymphocytic leukemia patients with CAR-T therapy, which uses the body’s own immune system to fight cancer. In a paper published Wednesday [last February]  in the journal Nature, researchers report that their first two patients were still cancer-free 10 years after their treatment. What’s more, the cells were still present, protecting against future lymphoma invaders.”

     “….The therapy’s effectiveness and longevity are “beyond our wildest expectations,” one of the doctors told reporters Tuesday.”

      So:  What exactly is CAR-T therapy?

      “Chimeric Antigen Receptor (CAR) T therapy genetically modifies the body’s T-cells — the white blood cells that play a lead role in the body’s immune response to foreign particles — to attack cancer.”   In this therapy, the body’s own T-cells are removed, genetically modified  (with the help of mice – see below)  to create a kind of combined T-B cell, and then re-injected into the body.  These cells are primed to attack leukemia cells in the blood and kill them” – like Special Forces sent on a mission.

     What is most amazing – normally, the body’s own immune system will attack anything that is not totally human, totally familiar to the body itself.  But in this case, somehow, the immune system tolerates the CAR-T cells – and they quickly begin to multiply.  It’s like having an army of soldier cells that attack and kill leukemia cells on sight…and they reproduce rapidly…and forever!   

      This is indeed a cure for leukemia!  

         Gantz reports, “Doctors don’t use words like cure lightly or, frankly, very often,” said David L. Porter, the director of Cell Therapy and Transplantation at Penn. “When we started this, I don’t think we were expecting this would develop into such a powerful curative therapy.”

.  . . . . . .

      About 24,000 people die of leukemia yearly in the US – more men than women.  It is true that most cancer deaths (90% of them) are caused by ‘solid cancer’ (tumor-related).  But immunotherapy treatment for them, too, is being intensively researched and holds promise. 

         CAR T cell therapies are at present hugely expensive  — $375,000 to $475,000 per treatment.  This is because manufacturing them is expensive and because administering them requires extensive monitoring for fear of CRS  cytokine response syndrome (the kind of immunological ‘storm’ that has resulted from COVID-19, for instance).     But the cost will come down over time.

   How have mice helped?

   A National Institutes of Health (NIH) study reports:  “We established a humanized mouse (hu-mouse) model with a functional human immune system and genetically-matched (autologous) primary acute B-lymphoblastic leukemia (B-ALL) that permits modeling of CD19-targeted CAR T cell therapy in immunocompetent hosts without allogeneic or xenogeneic immune responses.”

     A humanized mouse!   With human leukemia B-cells.  Which are then killed by CAR-T cells.  Without endangering humans, in the early trials. 

     We have pigs providing heart and kidney transplants.  And mice providing in-vivo tests for new leukemia treatments. 

     Thanks guys.