Chimeric antigen receptor, or CAR-T, therapy is a proven tool in the battle against hematological malignancies. But while this relatively new form of immunotherapy has been shown to keep certain types of blood cancer at bay, it hasn’t yet been shown to eradicate solid tumors.
However, new data indicate that CAR-T therapy may be effective against some solid tumors when used in conjunction with an mRNA vaccine. At the 2022 American Association for Cancer Research conference, new research was presented, suggesting that the combination of CAR-T therapy and a BioNTech mRNA vaccine may offer a promising treatment for lung and kidney cancer.
Thanks to the COVID-19 pandemic, mRNA vaccines have made headlines in recent months. BioNTech worked with Pfizer to develop an effective COVID vaccine; before the pandemic, the firm focused on the use of mRNA vaccines in cancer treatment. Clinical trial data shared at the AACR conference show potential for treating solid tumors through a combination of mRNA vaccines and CAR-T cell therapy.
How Does CAR-T Therapy Work?
CAR-T optimizes patients’ own T-cells, which are white blood cells that fight infections in the bloodstream. In the lab, T-cells are modified to contain synthetic proteins known as chimeric antigen receptors. When reintroduced into the patient’s body, the re-programmed T-cells seek out, identify and attack proteins known as antigens, which are found on cancer cells.
Over time, the T-cells remain in the body where they continue to multiply. As the patients’ optimized T-cells circulate, they eradicate targeted cancer cells. This type of immunotherapy can offer years-long defense against cancer, using a patient’s own cells.
In the past, CAR-T cell therapy has only been found to be effective in treating leukemia, lymphoma and myelomas. But new research incorporating mRNA vaccine technology shows promise for treating other types of cancer, including solid tumors.
mRNA Vaccines and CAR-T Therapy
In clincial trias at the Netherlands Cancer Institute, researchers used patients’ T-cells to identify and attack a protein known as claudin-6 or CLDN6. This tumor-specific antigen is often found in solid tumors.
Then the patients received an mRNA vaccine designed to target CLDN6. In clinical trials, the reprogrammed cells entered (and remained) in solid tumors. Of the 14 patients evaluated, six experienced shrinking or even disappearing tumors. One patient in the trial had been in remisison for almost six months by the time the research was presented at the conference.
In the past, treatment with CAR-T therapies has usually hit two stumbling blocks: Either the reprogrammed cells can’t enter a solid tumor, or when they do, they simply don’t persist long enough to do their job. Results of the Netherlands Cancer Institute trial seem to overcome these issues, indicating promise for future treatment methods.
Of course, the research is still in early stages. More study is needed, including larger trials with more participants. Questions remain as to potential off-tumor toxicity associated with long-term treatment at higher doses. It’s also not clear if simply boosting CAR-T therapy with mRNA vaccines alone is enough to fully clear solid tumors.
Though the trial results are preliminary, the combination of CAR-T cell therapy and mRNA vaccine technology shows the potential for promising new treatments on the horizon.