In the last few decades, scientists have finally learned to harness the immune system to successfully treat cancer. Image for Representation.
| Photo Credit: Freepik
In the last few decades, scientists have finally learned to harness the immune system to successfully treat cancer. Although doctors often use immunotherapy drugs, another type of treatment uses patient’s cells to treat their own cancers.
Car-T therapy, short for “chimeric antigen receptor T-cell”, is a cutting-edge treatment that reprogrammes a patient’s immune cells to fight their cancer. This innovative approach involves taking T-cells, a type of white blood cell that plays a crucial role in the immune system, from a patient and modifying them in a laboratory to better recognise and attack cancer cells.
These enhanced T-cells are then multiplied and infused back into the patient, where they seek out and destroy cancer cells. Lots of data shows that in difficult-to-treat lymphomas, a type of cancer, patients can do so well.
In November 2023, the US Food and Drug Administration (FDA) announced an investigation into this celebrated cancer treatment. They were looking into whether Car-T therapy might be causing new cancers in some patients who had undergone the treatment. This was a significant concern given the therapy’s reputation as a revolutionary cancer-fighting strategy.
Initially, the FDA mentioned that it had observed 20 cases where patients developed new immune-cell cancers, such as lymphomas or leukaemias, which are types of blood cell cancer, after receiving Car-T therapy. This prompted questions about who these patients were, how many such cases existed and what other treatments they might have received before Car-T therapy.
By March 2024, the FDA had documented 33 such cases among around 30,000 treated patients. Consequently, all Car-T therapies now carry a boxed warning about the potential risk of developing secondary cancers. The European Medicines Agency also started its own investigation into the matter.
Despite these concerns, it is still unclear whether the new cancers are directly caused by the Car-T cells or whether other factors are involved. It is also important to note that these cancers are very rare – as data published this month shows.
Many cancer treatments come with a risk of secondary malignancies and, of course, the cancer returning. And patients receiving Car-T therapy often have had several other treatments that could also contribute to the risk. Researchers are now working to determine if Car-T therapy is a contributing factor or the primary cause of these new cancers.
Car-T therapy was initially used for patients with no other treatment options, but it has since been approved as a second-line treatment for certain types of blood cancers, like lymphoma and multiple myeloma. Scientists are also exploring its potential for treating solid tumours including hard to treat brain cancers, autoimmune diseases, ageing, HIV and other conditions.
The process of creating Car-T cells involves using viruses to insert new genetic material into T-cells. These viruses, called retroviruses, are engineered to carry the gene for a chimeric antigen receptor (Car) into the T-cells.
Massive benefits
While these retroviruses are modified to be safe, there is always a risk that the new genetic material could disrupt other important genes and potentially lead to cancer – a phenomenon known as “insertional mutagenesis”. This means new genetic material is added to a cell.
This risk isn’t new. About 20 years ago, gene therapy treatments for severe combined immunodeficiency syndrome using similar retroviruses led to leukaemia in some patients. As a result, scientists have worked to improve the safety of these viral vectors. The FDA now requires thorough testing to ensure that the viruses used in Car-T therapy cannot replicate and cause harm.
Despite these findings, the most important thing to emphasise is that secondary cancers remain rare and these cell therapies can have massive benefits in very sick people.
The new review of patients treated with Car-T therapies at various centres found that only a small percentage developed secondary cancers, and most were not the type directly linked to the Car-T treatment. This suggests that while there is a risk, it is relatively low compared to the immediate threat posed by the patient’s existing cancer.
Medical professionals now inform patients about the potential but rare risk of secondary cancers when discussing Car-T therapy. For most patients, especially those with advanced cancers, the potential benefits of Car-T therapy far outweigh these risks.
As mentioned, Car-T therapy is also being investigated for other applications beyond cancer. For instance, it has shown promise in treating autoimmune diseases such as lupus and even in preventing organ transplant rejection. The potential uses for Car-T cells are continually expanding, offering hope for treating a wide range of diseases.
Ultimately, while the risk of secondary cancers from Car-T therapy is a serious consideration, the benefits for many patients are significant and far outweigh this small risk. Research will continue to refine these treatments and improve their safety.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
