Latest data: Memory NK cell therapy can overcome TME, and is expected to overcome a variety of NK-resistant solid tumors

October 24, 2022 /eMedClub News/--Recently, immunology company INmuneBio presented its preclinical data of memory NK cell therapy INKmune, which showed that INKmune can convert patients' normal resting NK (rNK) cells into effective memory-like NK cells.
These cells are able to overcome immunosuppression associated with the tumor microenvironment (TME) and exhibit stronger anti-tumor activity
.
Based on preclinical data, the company believes that many solid tumors that are currently resistant to NK cell killing are expected to be overcome
by INKmune.

The immunosuppressive state of the tumor microenvironment is one of the important reasons for the failure of cell therapy to treat tumors, and in recent years, many studies have been focused on improving the therapeutic effect
by targeting and remodeling the tumor microenvironment.
In solid tumors, cell therapy is more difficult to kill because of the obstruction of the tumor microenvironment, because the tumor microenvironment oxygen content is low and there is immunosuppression, cell therapy must overcome these adverse factors in the tumor microenvironment to play a role in the treatment of solid tumors
.

According to the results of preclinical research, INKmune transforms the patient's rNK cells into memory-like NK cells, which can overcome the problems of immunosuppression and hypoxia in the immune microenvironment, directly target solid tumors and play a killing role
。 In addition, INKmune was able to activate NK cells from the patient and from healthy donors, and compared with pre-treatment with INKmune, the memory-like NK cells activated by INKmune showed stronger anti-tumor activity and were able to kill and lyse a variety of solid tumors that were resistant to NK cell killing, including ovarian, prostate, kidney and nasopharyngeal cancers
.

The table below shows the percentage of tumor cells killed by different types of
NK cells.
For example, it has been laboratory determined that healthy donor-derived rNK cells kill less than 4% of DU145 prostate cancer cell lines within 4 hours, while INKmune-activated NK cells kill approximately 66% of DU145 prostate cancer cells
in the same amount of time.
The negative value means that tumor cells grow faster than NK cells, and NK cells activated by INKmune show strong anti-tumor activity
in many different types of cancer cells.

In order to determine which protein upregulation was specifically triggered by INKmune, the researchers compared NK cells activated by IL-12, IL-15, and IL-18 cytokine
mixtures with INKmune-activated NK cells.

It was found that 141 of the 250 proteins with the highest levels were specifically induced by INKmune, and the expression of these proteins was not affected by the cytokines IL-12, IL-15, and IL-18.

These unique proteins are closely related to cell metabolism and may be the key to inhibiting the immunosuppressive effect of
the tumor microenvironment.

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Another company is Memory NK Cell Therapy

Coincidentally, Wugen, a recent cell therapy company, also demonstrated preclinical data
from a memory NK cell therapy WU-NK-101 at ESMO conference.
WU-NK-101 is an allogeneic memory NK cell therapy developed by Wugen using its proprietary MonetaTM platform, with unique, more potent anti-tumor activity and cytokine-induced memory-like (CIML) phenotypes
.

Preclinical data show that WU-NK-101 overcomes some limitations associated with NK cell therapy for solid tumors, and shows better transport capacity and adaptability in the immunosuppressed tumor microenvironment compared with traditional NK cell functional characteristics, as well as enhanced function under immunosuppressive TME conditions to support its application
in solid tumors.

In vitro, a statistically significant increase in antibody-dependent cytotoxicity (ADCC) was observed when WU-NK-101 was used in combination with monoclonal antibodies compared to monoclonal antibodies alone; In addition, the antitumor activity of this combination therapy compared to WU-NK-101 alone has been further validated
.

Overall, these data suggest that WU-NK-101 may overcome many of the limitations of current cell therapies and show strong potential
in the field of solid tumors and combination therapies.

epilogue

In general, memory NK cell therapy has become an innovative direction in the NK cell track, and its preclinical data has shown strong potential
in the field of solid tumor treatment.
In addition, NK cell therapy has triggered a boom in layout due to its unique advantages, according to a report published in Nature Reviews Drug Discovery in June 2022, researchers took stock
of the global anti-cancer cell therapy pipeline and clinical development status.
The results found that as of April 15, 2022, there were 2,756 cell therapies in active development in the global immuno-oncology pipeline, an increase of 36%
over the same period in 2021.
Growth in natural killer cell (NK) therapies is 55%
higher than last year.

While the pipeline has grown significantly, the innovative direction and novel technology platform of NK cell therapy have also increased significantly
.
However, there are still some challenges in the development of NK cell therapy, including in vitro expansion difficulties, durability, and transfection efficiency to be improved
.
With the application of innovative technologies such as iPSC technology and CRISPR genome editing technology, some difficulties in this field will eventually be effectively solved
.

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