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Off the Shelf Cellular Therapy for Chronic Lymphocytic Leukemia (CLL)?

In science and medicine, information is constantly changing and may become out-of-date as new data emerge.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.

We have reported on the justified excitement about CAR-T therapy, especially now with the recent FDA oncology board recommendation for approval of CAR-T for acute lymphoblastic leukemia (ALL) (see: http://cllsociety.org/2017/07/fda-panel-recommends-approval-gene-altering-leukemia-treatment/)

But the science isn’t stopping there.

There is new research that uses modified chimeric antigen receptor (CAR) natural killer (NK) cells from unrelated umbilical cord blood and helping them to find and destroy the CLL instead of pulling off the patient’s own T cells and modifying and expanding those cells.

The CAR-NK cells seem to work for mice with a model of chronic lymphocytic leukemia.

A clinical trial is open now at MD Anderson to treat CLL and other related B-cell malignancies.

See: https://clinicaltrials.gov/ct2/show/NCT03056339?term=NCT03056339&cond=CLl&rank=1

It makes perfect sense.

Umbilical cord blood has been used for transplants as its hematopoietic stem cells are much more forgiving in terms of having to be tightly matched from donor to recipient. When a matched donor, either related or unrelated cannot be found, a cord donor can be a life-saving option when a transplant is the patient’s last best chance with a lower risk of graft versus host disease.

And wait, the story gets better.

It seems that natural killer cells may not need to be matched at all.

From the article:

Rezvani and Shpall have given patients cord-blood derived NK cells in a variety of clinical trials and found that they do not cause graft vs. host disease, therefore don’t have to be matched. NK cells can be an off-the-shelf product, prepared in advance with the necessary receptor and given promptly to patients.”

Compare this to the highly individualized need to modify, expand, and give patients back their own T cells, a process that takes weeks and doesn’t always work.

Off the shelf “CAR-NK” would be cheaper, faster, and easier.

“CAR NK cells are scalable in a way that CAR T cells are not,” Rezvani noted.

Wait, there’s still more.

It turns out that the cord NK cells are even better killers than the patient’s own NK cells.

This too makes sense as our immune system with CLL is compromised.

We have long known that our T-cells are “exhausted’ and lousy cancer fighters. The proven benefit of ibrutinib with CAR-T therapy for CLL may be related to how it changes the T cell repertoire to be more functional and better attack the cancer.

So what is the catch?

NK cells don’t have memories like T cells and they are not long lived. The concern is that the chronic lymphocytic leukemia will relapse when they NK cells die off. They are working on ways to make these CAR-NK live longer. However, we are already seeing relapses with the much longer-lived CAR-T cell therapy when the CAR-T die off.

To read more, see: See https://medicalxpress.com/news/2017-07-genetically-cord-blood-derived-immune-cells.html

Brian Koffman, MD 7-18-17

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