For the Sake of Science

There are two foundational concepts a person must understand before he can say he understands biology. First, all life has evolved from a common ancestor via natural selection. Miss this concept and one has no reference frame for anything within the entire field. It would be like trying to grasp physics without understanding gravity. Second, it’s all about shape. This can apply to many other fields, but it is an essential concept within biology. The molecules within living organisms are like pieces of a puzzle, or like keys and key holes. However one wishes to think about, biology really is about shape. Now with that in mind, I turn to some really awesome cancer research.

[Bruce] Levine and his colleagues designed a new gene that can be inserted into T cells to trick them into attacking cancerous B cells, the cause of chronic lymphocytic leukemia (CLL). The new gene encodes a receptor that, on one end, can bind to a molecule that’s unique to cancerous B cells. The other end of the receptor sets off a chain reaction when such a B cell is bound, eventually leading the T cell to destroy the cancerous cell. “Essentially, we’re converting T cells that would normally recognize other types of cells to be tumor specific,” Levine says.

In many ways, this is very much a basic immune response. The difference here is that gene transfer techniques have been used to modify the shape of the T cells to recognize particular cancerous cells, something which does not normally happen. As the article states, one patient went from having 170 out of 200 cells containing a cancer-causing mutation to having all signs of his leukemia vanish. The paper itself goes further and says tests showed 198 out of 200 cells to be negative for that mutation, which is within the normal range for such tests.

The insertion of these modified cells was not without complications. The cells themselves are without toxicity, but within two weeks the patient was experiencing a low-grade fever and chills, both of which intensified and required a short hospitalization. He also had tumor lysis syndrome, which could be expected – and is ultimately a good thing. It’s a common condition after certain types of cancer treatment (though it had not previously been reported in cellular immunotherapy). Basically, cell lysis is when a cell is destroyed and its contents spill out. Often, this constitutes a significant release of chemicals which cause a reaction. It can be quite dangerous, but then, so is cancer.

While this research is cause for a lot of excitement, I think, there also must be much reservation. The test subjects number a whopping three patients. Furthermore, they’ve only been tracked for approximately a year since treatment. It is fortunate that they still contain within them cells with the inserted gene – it’s self-propagating since it gets passed on with somatic division just like any other gene – but more time needs to pass before too much more can be said (not to mention the dramatic need for a much larger sample). There is also concern that there could be long-term deficiency of B cells in patients since the genetically modified cells do attack normal B cells as well as the cancerous ones. These are all things that can be clarified with continued research – and I’m confident “with continued research” is a phrase that is more than traditional lip service, in this case.

Filed under: Biology | Tagged: Adam Bagg, Bruce L. Levine, cancer, Carl H. June, CD19, Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia, David L. Porter, Leukemia, Michael Kalos, Serial Killer immune cells |