– By Ramon Valencia, Vice president-Corporate Development & Strategy –
The focus of immunotherapy over the last decade has been activating or re-activating T cells. A lesser known, but no less important to healthy immune function, is an immune cell called a natural killer (NK) cell. .
NK cells “natural killer” are named so because they can be removed from the body and are able to immediately kill infected cells or tumor cells without prior sensitization. NK cell can attack any cell that it recognizes as infected, transformed, or damaged. They are part of the innate immune system and are thought to have evolved to protect us and survey their environment for stress or viral proteins in a process called immunosurveillance.
New avenues – Therapeutic applications with NK Cells
NK cells are experiencing something of a renaissance these days. For example, researchers at the Sloan Kettering have discovered that NK cells play a role in metastatic latency. This means that they help keep rogue cancer cells in check and prevent the cancer from growing and spreading.
Moreover, researchers at the University of California, San Francisco (UCSF) found that the presence of NK cells in a tumor may help explain why some people respond to certain types of immunotherapy while others do not. They analyzed human tumor samples provided by their clinical collaborators for the presence of NK cells, and found that the presence of NK cells in tumors was correlated with elevated numbers of protective stimulatory dendritic cells, as well as long-term patient responsiveness to immunotherapies known as anti-PD-1 drugs, and to overall patient survival. *
So what sets NK cells apart from other immune cells?
NK cells have two main ways of taking out threats:
- By detecting the presence of stress signals emitted by cells in trouble, including cancer cells; these stress signals cue NK cells to kill them.
- By recognizing cells that lack identifiable markers of “self.” Each of our cells has a molecule on it called MHC that differentiates our cells from other people’s cells. NK cells seek and kill cells that lack MHC, which in some cases means cancer cells. Cancer has evolved to trick T cells by removing MHC molecules from their surface. This allows the cancer to fly under the radar of T cells, which require MHC for their action. Luckily, removing MHC makes cancer cells vulnerable to killing by NK cells.
Updating the Dogma
Historically, textbooks refer to NK cells as part of the innate immune system. This is the system of immune defenses that are present from birth and are always active. Innate immune cells are good at stopping invaders at the gate, but they don’t stick around after a fight, and they don’t learn from past experience.
According Dr. Joseph Sun at Memorial Sloan Kettering Cancer Center, that description doesn’t apply very well to NK cells because NK cells remember, and they can persist in the body for long periods of time. This makes them more like the T or B cells of the adaptive immune system. It makes sense: NK cells, T cells, and B cells all develop from the same precursor cell, called a common lymphoid progenitor. They’re basically siblings.
NK Cells in Immunotherapy
Cancer therapeutics companies have begun exploring the use of NK cells in cancer immunotherapy. The activation of NK cells in the tumor allows the NK cells not only to eliminate tumor cells but also release cytokines that stimulate dendritic cells which in turn recruits and activates T cells. This concerted immune activation results in robust anti-tumor immune response and extends patient survival. Zumutor is developing novel antibody drugs that interfere with NK cell immune checkpoints and lead to tumor suppression.