Natural killer cells: the next frontier for cancer treatment

Natural killer (NK) cells are an important component of immunity, for their ability to destroy cells infected with viruses as well as those containing cancer tumors. From the same family as T and B cells, they differ from T cells as they do not require an antigen to kill cancerous cells.

US biotech company Cytovia Therapeutics is developing next-generation oncology treatments using these cells. Cytovia’s CEO Dr Daniel Teper tells us more about this emerging area of cell therapy, challenges to its development and how it compares to CAR-T cell therapy.

Pharma IQ: How is the increased demand for cell therapies influencing drug research?

Daniel Teper: We need to increase the access, safety and affordability of effective treatments for many more patients. CAR-T cells have shown blockbuster outcomes for patients with blood cancers, however, the risk of side effects including cytokine release syndrome (CRS) and graft-versus-host disease (GVHD) as well as a nationwide shortage limits their use.

Pharma IQ: How complex is the manufacture of CAR-T cell therapies compared to other types of treatment?

DT: The CAR-T shortage problem was recently laid out from a clinician and patient perspective in an article entitled “How do you decide? Cancer treatment’s CAR-T crisis has patients dying on a waitlist.” There are FDA-approved CAR-T cells for multiple myeloma, but these are personalized to each patient and require hospitalization.

There are limited hospital spots – even at major medical centers, there are less than five slots per month. Additionally, the manufacturing timelines of weeks are longer than acceptable for most patients that may progress over that period. These critically ill patients that have failed three lines of therapies are left waiting for a slot and 20 percent die while waiting.

Currently, marketed personalized CAR-T cell therapies are challenging to make, take too long to make, not enough are being made, and the therapies are considerably more expensive compared to other modalities – small molecules and antibodies, among others. Solutions to these challenges are needed.

Off-the-shelf adaptive and immune cells could make manufacturing more scalable and democratize access to these much-needed therapies. These therapies are only now starting to advance into clinical trials and all the downstream go-to-market issues are unknowns right now.

Pharma IQ: What is Cytovia doing in this field?

DT: Over the past decade, immuno-oncology has emerged as the novel approach to cancer treatment through the stimulation of the body’s own immune system to kill cancer cells. We are aiming to overcome the limitations of the first wave of immune cell engineering based on T cells and CAR-T therapies, as we are focused on leveraging another type of immune cell called natural killer (NK) cells which have differentiated functions compared to T cells. These will likely become the next transformative therapeutic opportunity in the next two to five years.

We built Cytovia as the first company to have two complementary therapeutical platforms: a cell platform capable of generating unedited and gene-edited natural killer cells differentiated from stem cells (iNK cells) and an antibody platform capable of generating trifunctional antibodies that boost the activity of NK cells (Flex-NKTM cell engagers).

Both platforms generate therapeutics that are patient agnostic, meaning our therapies can be given to any patient when requested without the need for engineering each individual’s cells. The cell therapy field refers to this as “off-the-shelf therapeutic” and enables higher affordability and faster access to cancer treatments.

Pharma IQ: What other challenges do you envisage and how do you see this area of pharma evolving over the next five years?

DT: We aim to develop next-generation cell therapies that will have higher efficacy and better safety profiles. NK therapeutics are very promising in this regard compared to T-cell therapeutics because they use not only adaptive, but also innate immunity mechanisms. Another frontier is to design cell therapies that will target solid tumors. This has been a conundrum across the industry and so far many people are scratching their heads.

The big proof-point was supposed to be Tmunity, founded by CAR-T pioneer and Nobel Laureate Dr Carl June. Unexpectedly the company had to terminate its lead CAR-T cell program for prostate cancer after two patients died; the company has nearly gone dark and investors are hesitant to invest in the peer group. NK therapeutics seem to be more promising in this regard and at Cytovia we are indeed developing two programs on solid tumors.

Among the challenges but necessary goals, we should aim to select patients that are more likely to respond to these novel therapies, and this is a challenge for medicine as a whole – often therapies do not show effectiveness simply because the sensitive patient population has not been properly selected.

Quick links: 

• The latest in cancer treatments: Recreating the tumor environment
• Sanofi announces partnership to develop new class of oncology therapeutics
• Connecting quality data to overcome pharma’s toughest challenges

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