Is the re-birth of blood heavyweight CAR-NK more effective than CAR-T cell immunotherapy?

Guide: Natural killer cells (NK cells) are important immune effect cells in the body.
after being activated by IL-12, IL-15, and IL-18, NK cells can differentiate into cytokine-induced memory-like (ML) NK cells, which will also exhibit stronger anti-tumor activity.
in this study, researchers combined CAR genetic engineering with NK cells to increase the response of NK cells to drug-resistant leukemia/lymphoma, and the results showed that CAR-ML NK cell therapy may be safer than CAR-T cells! Current tumor immunotherapy, such as Anti PD-1, PD-L1, and cellular immunotherapy, are mostly focused on activating the patient's own immune system (T-cell activity) to attack tumor cells.
however, not all cancer patients respond to this type of immunotherapy, so scientists have been looking for new cancer immunotherapy strategies that can improve the effectiveness of immunotherapy for years.
Figure 1: On July 2, 2020, a new study published online in the Journal of Blood, "CAR-modified memory-like NK cells potent responses to NK-resistant lymphomas," a team of researchers from the University of Washington School of Medicine combined two strategies of immunotherapy, CAR (embedded antigen receptors) and MNK cells, into a new therapy, CAR-ML NK cell therapy.
In treating blood cancers such as leukemia, studies of human cells and mice have shown that the treatment is more effective than US alone with CAR or memory-like NK cells, and that the new treatment may be safer than CAR-T.
CAR-NK cell therapy has many advantages, starting with CAR-T cells, which retain the intine ability to identify and target tumor cells through their natural receptors, thus reducing the likelihood that tumor cells will be able to escape injury when treated with CAR targeting.
, CAR-NK cell therapy, in several clinical trials, has shown that immune rejection does not occur for days to weeks.
therefore, CAR-NK cell therapy does not exhibit similar safety problems compared to many clinical trials of CAR-T cell therapy, such as the absence of cytokine release syndrome.
, NK cells do not require a strict HLA match and therefore do not cause graft-resistant host disease, which is a significant advantage of CAR-NK cell therapy and a significant risk for CAR-T cell immunotherapy.
Figure 2: CAR-NK Production Process: CAR-ML NK cells or can be used to treat solid tumors In this study, researchers assigned CAR genetic engineering modification to ML NK cells, resulting in immunotherapy combining the benefits of CAR and NK.
, the study found that CAR-ML NK cell therapy was less likely to have toxic side effects such as cytokine storms, neurotoxicity, etc., leading to the view that CAR-ML NK cell therapy is safer.
. Todd A. Fehniger, author of the paper, said: "Immune therapy offers great hope in cancer treatment, but we need more effective and safer immunotherapy.
based on a treatment strategy developed for leukemia patients using NK cells, we established this binding method.
The combination increases the ability of NK cells to attack cancer cells, while also using the genetic engineering methods of CAR cell therapy to direct NK cells to tumor targets that are often overlooked, fundamentally changing the types of cancers that NK cells can treat, including other blood cancers and some solid tumors."
" ML NK cells stem from the discovery of anti-tumor activity in patients' self-contained NK cells ML NK cells, as a result of previous research by the team.
Fehniger team collected the patient's own NK cells, using specific cytokines to induce differentiation, and found that NK cells could actively attack tumors after differentiation.
then injected these treated NK cells back into the patient for treatment.
results show that this induction allows NK cells to form memories when they are resistant to tumors, and when these cells are returned to the body, they are more effectively targeted at tumor cells, so the researchers call them memory-like (ML) NK cells.
in a small clinical trial at Barnes-Jewish Hospital, ML NK cells were able to provide continuous remission to some leukemia patients, but not everyone was effective, and some tumor cells escaped the damage of ML NK cells.
, the researchers used genetic engineering to customize CAR-ML NK cells, giving ML NK cells the ability to recognize tumor cells.
animal experiments, treating leukemia mice with car-memory-NK cells was more effective than using memory-like NK cells alone, and treated mice survived longer.
addition, the treatment of CAR-ML NK cells with relatively lower doses still has a welcome effect.
Figure 3: CD19 CAR-ML NK cells for the treatment of leukemia mice CAR-ML NK cells prospects Co-author Dr. Melissa Berrien-Elliott believes that heteroglycerogenic NK cells can be amplification in severe immunodeficiency mice to achieve effective anti-tumor activity, which in itself is a major breakthrough, breaking the traditional CAR-NK in the body can not achieve an effective multiplier bottleneck.
, smaller doses of CAR-ML NK cells can effectively control tumor growth, which may allow CAR-ML NK cells to convert more quickly to clinical applications.
On the other hand, since CAR-NK cell immunotherapy rarely produces serious toxic reactions, CAR-ML NK cell immunotherapy can be applied early in cancer due to the strong anti-tumor activity of CAR-ML NK cells.
Although other research teams have developed CAR-NK cells, most of these NK cells come from NK-92 cells or are synthesized by stem cell induction, rather than from adult constellations or the patient's own NK cells, which is the biggest difference and advantage of the therapy shown in this study.
the author's message that "other cell therapies that artificially differentiate stem cells into NK-like cells do not guarantee that these differentiated cells have all the characteristics of mature NK cells."
And our program uses mature NK cells, which have been shown to be effective in certain types of cancer patients, especially leukemia patients, and induced memory characteristics that increase the durability and effectiveness of these cells to multiple cancers," Dr. Fehniger said.
" Figure 4: Fehniger Team Source: Supplied: 1. Gang, M., et al., CAR-modified memory like-NK cells exhibit potent responses to NK-resistant lymphomas. Blood, 2020.2. Pfefferle, A. and N.D. Huntington, You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy. Cancers (Basel), 2020. 12(3). YT. Lin source: WeChat public number BioImmunology !-- end of the content display -- !-- to determine whether the login ends.