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CAR-T Part 1

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Take Away Points:

  • CAR-T (Chimeric Antigen Receptor T-cell) is a cellular immune therapy using our own T cells that have been educated to recognize and attack our cancer.
  • The target of the educated T cells is CD19 that is found on all mature B cells including normal B cells.
  • With this CAR-T therapy, there may be lifelong loss of all B cells and thus of any antibody production.
  • It has generated some dramatic responses about half the time in very tough to treat CLL cases that had rum out of options.
  • We are very early in our experience with CAR-T therapy.

Preface:

Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting.  With time and experience, you’ll become familiar with the terminology and acronyms.  We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We have provided a glossary and a list of abbreviations and acronyms for your reference. 

CAR-T Therapy:

As discussed previously in our article on cytotoxic T cells and this amazingly cool NIH (National Institute of Health) movie on cytotoxic T cells, excitement is growing about immune cellular therapy. After all, the only “cure” for CLL has been a cellular therapy, namely getting a new immune system through a bone marrow or hematopoietic stem cell transplant (HSCT).

CAR-T therapy removes all the inherent risks of importing someone else’s immune cells.

As Dr. David Porter from the University of Pennsylvania explains, CAR-T stands for C chimeric (from the Greek mythological chimera or fire-breathing monster that was an unholy mix of several animals, but in cellular therapy refers to an organism having two distinct genetic signatures), A– antigen or a distinct identifying protein on a cell’s wall, R– receptor, and T- for T- cell, the type of lymphocyte that is involved in cellular immunity.

Let’s listen to Dr. Porter in Part 1 of a two part interview recorded in Greece in late 2014 at the International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment.

Here is a link to the journal Blood that describes the steps in the CAR-T process.

  1. Step 1 is the removal of T cells and is self-explanatory, similar to donating platelets.
  2. Step 2 involves the infection of the patient’s T cells in the laboratory with a virus that is able to easily penetrates the T cells and insert the genetic material to allow the transfected (a cell that has had foreign nucleic acids introduced) cells to recognize the target cancer cells.
  3. Step 3 is the re-infusion of the T cells back into the patient. Please note that it includes lymphodepleting therapy (usually chemotherapy to reduce or “deplete” the number of lymphocytes), normally done in advance of this cell transfer to give the new CAR-T cells a fighting chance. CAR-T is done in addition to chemotherapy, not instead of chemotherapy.
  4. Step 4 is the monitoring for any problems including the dangerous and possibly therapeutically critical cytokine (small proteins that direct communication and behavior between cells) release syndrome or “storm” that is described in the second part of this article.

CAR-T therapy is a very promising and exciting but complicated and experimental option as of today.

Brian Koffman 3/1/15 with help from SA

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