Using Gene-edited Killer Cells to Target Cancer, Endometriosis and Beyond

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Australian biotech company, Cartherics, is pioneering a new generation of cell therapies aimed at treating solid tumours, endometriosis, and potentially even neurological diseases. Improving on the traditional Chimeric Antigen Receptor (CAR) T-cell approach, the company uses gene-edited natural killer cells to better navigate the complex tumour microenvironment.

In this Q&A, CEO and Executive Director, Professor Alan Trounson shares how Cartherics' unique approach could address major gaps in current treatments, and why careful, considered progress is key to building truly transformative therapies.

Commencing with pioneering work in the late 1990s and leading to the first product approvals in the mid-2010s, CARs have been inserted into the genome of patient's own extracted T cells using viral vectors.  The CAR would direct the T cell to target an antigen on the surface of the tumour that was being targeted; most commonly CD19, which is a B cell antigen. The efficacy observed was extraordinary for a cancer treatment, where an 80 to 90 percent response rate was reported for patients, and after five years, 30 to 40 per cent of patients remained clear of cancer.  

Since then, other antigens have been targeted, but mostly in blood cancers. CAR-T cells are  relatively efficient in controlling many lymphomas and leukemias, but in solid tumours, which represent the majority of cancers, there has been very little success, certainly not in the same way as there was for blood cancers. Control of solid tumours remains a major challenge.

We developed the preclinical data for an autologous CAR T cell to treat ovarian cancer (which is in development through partners), but we decided to focus on an allogeneic CAR product using gene edited induced pluripotent stem cells (iPSCs) that were derived from umbilical cord blood donors. We could precisely edit the CARs into the iPSCs, and begin to work our way into combating the inhibitory tumor microenvironment (TME) that prevents immune cell killing of the abnormal cancer cells.  

Probably the best examples of overcoming this inhibitory TME are the checkpoint inhibitors that were developed as monoclonal antibodies against PD1, PDL1,CDLA-4 and LAG3. These monoclonal antibodies block negative (immunosuppressive) signals between tumours and the patient's immune cells, allowing them to very effectively destroy cancers in some patients. We were using natural killer cells instead of T cells because they have an excellent safety profile. They're also more versatile killers of tumour cells because they have added killing components beyond the CAR. 

In addition to forming cytotoxic attack cells, you can also derive memory CAR-NK cells, so we're interested in actually having immune memory cells remain in the patients in case the same cancer or a similar cancer reappeared. 

As it turns out, some of the CARs that we've been using for cancer will also attack endometriosis, particularly advanced endometriosis, because endometrial cells express the same antigens on their surface. For ovarian cancer, we plan to administer the NK cells directly to the pelvic cavity; the same route of administration would also be applicable for  severe cases of endometriosis.

I think all of the adenocarcinomas - that is cancers of the major organs - are susceptible to our CAR-targeting approach. For example, pancreatic cancer, prostate, gastric or lung cancer could be targeted. We're trying to stay focused on ovarian cancer because there are  few effective treatments available, so there's a strong desire and need for patients to receive our novel treatment. 

This type of approach is pretty interesting for many different conditions. Some CAR-T companies are pivoting to treat autoimmunity, which we're not, but it does look interesting. The control of fibrosis is also under study because you can target the particular antigens present on fibrotic tissues in animal models. 

Our other areas of interest are using the same approach for some neurological diseases such as Alzheimer's Disease or traumatic brain injury. I have a lot of friends with Alzheimer’s and Parkinson’s Diseases that are suffering because of the lack of effective therapy.  Traumatic brain injury from accidents or concussions is another area of very large unmet need of therapy. Emerging data indicate that NK cells may be able to play a role in treating and controlling these complex diseases. 

It’s the opportunity to explore these other areas that I think makes our company rather unique, and that’s supported by having a strong discovery team in house with great academic partners.

I think we should be able to initiate clinical trials for our lead allogeneic product for ovarian cancer in 2026 or early 2027. We're in a fortunate position where we have a strong pipeline of innovative therapies in development, positioning us well to address unmet medical needs and drive long term impact. Entering the clinic entails a substantial commitment of the company’s resources. Too many companies push to the clinic too quickly in order to attract investments to keep them going, and I think that's the wrong thing to do. Racing into the clinic is understandable from an investor inspective but is very short-term thinking.  

We’re not rushing ourselves to the clinic with a single-purpose product, but rather trying to develop something that is really effective and has a chance to control solid cancers and other diseases.

We see ourselves as quite different to anybody else. We've maintained a very strong approach of using gene editing to craft our particular therapies and drawn in some highly effective blockers to TME immune cell inhibition, so it looks like we're going to be able to effectively treat solid tumours. What we've got is something that can actually be used in a number of different situations for different cancers and other conditions.  

I think we're a genuine discovery and development company looking to create products that are really effective for patients and that are desperately needed.

Watch their latest company video (above) and visit their investor page to discover how Cartherics are advancing innovative therapies and creating long term value.