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Could cord blood stem cell transplants be the cure for multiple myeloma?
I was diagnosed with multiple myeloma (MM) in early 1994. I underwent an autologous stem cell transplant (ASCT) in December of 1995. Autologous means that I used my own stem cells. It is safe to assume that there were MM cells hiding in my newly infused stem cells.
Not only did I relapse after my ASCT, I developed chemotherapy-induced cardiomyopathy in late 2010. The cardiotoxic chemotherapy from my ASCT damaged my heart.
I’ve been following stem cell transplantation for my cancer, MM, since 1994. ASCT does not provide longer overall survival aka OS. Yes, some patients who have an ASCT have a longer progression-free survival aka PFS. But ASCT comes with a host of short, long-term and late stage side effects.
Long story short, I live with an incurable blood cancer (MM), cardiomyopathy and several other nasty treatment-related health challenges. A possible therapy is cord blood natural killer stem cells.
We already know that the stem cells from the umbilical cord blood or UCB have the potential to treat various diseases – over 80 of them. We also know that the effectiveness of cord blood stem cells in treating some degenerative diseases is currently being explored.
The question that the researchers are asking themselves now is whether and how they can use the one particular type of stem cells known as natural killer (NK) cells to treat certain types of cancer. There are currently studies that are centered around determining the potential of cord blood NK cells to treat cancer by exploiting the unique ability of NK cells to target virus-infected and cancer cells. In this article, we will examine the role of cord blood natural killer cells in anti-cancer cellular immunotherapy and see whether and how they can be used to treat prevalent medical conditions.
First and foremost, let’s explain what cord blood natural killer (NK) cells are. We already mentioned how this type of stem cells is effective in targeting and killing cancer cells and cells infected with the virus. The way it works is the cord blood NK cells produce cytokines as a result of them exhibiting cytotoxicity towards such cells. NK cells are found in umbilical cord blood (UCB), which is a rich source of these cells.
Cord blood natural killer cells are cells of the immune system. They’re lymphocytes, just like T cells, which is why they’re often considered a cancer-fighting alternative to approaches that are based on the use of Treg or T-cells. The main difference between the two lies in the NK cells’ ability to eliminate target cells without being stimulated.
When it comes to the derivation of the natural killer cells, there are several platforms that need to be mentioned. First, there’s peripheral blood (PB), where NK cells are primarily found. The second platform that allows for sourcing of NK cells are induced pluripotent stem cells (iPSCs). Then, there is the third platform – the embryonic stem cells (ESCs). Finally, there’s the fourth platform for derivation of natural killer cells – umbilical cord blood (UBC).
One of the advantages of this last method of NK cell derivation is that the stem cells can be collected by the cord blood banking company during delivery and conveniently frozen for future medical and therapeutic use. The same can not be said for peripheral blood-derived natural killer cells. If the need for these stem cells arises, they will be easily obtainable thanks to cord blood banks securely storing the cells for the family that decides to preserve them.
“Cord blood (CB) offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT). The risk of relapse and graft vs. host disease after cord blood transplantation (CBT) is lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen mismatch.
Natural killer (NK) cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, and they play a significant role in protection against early relapse.
In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood.
Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors ligand mismatch and outcomes after CBT. Finally, we will touch on current strategies for the use of CB NK cells in cellular immunotherapy…
Natural killer cells have a remarkable potential to kill cancer as well as virally infected cells. They are the first cells to reconstitute after HSCT (8–14), they facilitate engraftment (78), they do not cause GVHD, and they may even prevent this complication by eliminating host antigen-presenting cells and donor alloreactive T cells (83, 123).
CB provides several distinctive benefits, and it is increasingly used as a source of CBT and cellular therapies. Resting CB NK cells are immature and are poorly cytotoxic compared with PB NK cells; however, these limitations can be overcome by ex vivo expansion using cytokines and feeder cells (48, 49, 52, 56, 124).
A number of clinical studies are evaluating the feasibility, safety, and anti-tumor efficacy of adoptive immunotherapy with CB NK cells. The biological mechanism and tempo of NK cell alloreactivity after CBT, especially with double unit CBT has not been fully elucidated. Before the immunological reactivity of NK cells and KIRs could be targeted and exploited to improve the response to CBT, we will need to have a better understanding of the biological mechanisms involved in NK-mediated anti-leukemia response.”