CAR-T therapies, best known for their use in certain blood cancers, could have a new application in the field of infectious diseases. A scientific review involving researchers from the Fundació Lluita contra les Infeccions analyses the available evidence on the use of this immunotherapy to treat severe infections. The study focuses on invasive fungal infections in immunocompromised people, in other words, those with weakened immune systems.
The article, published in Clinical Microbiology and Infection, is authored by Dr Pedro Puerta, Dr Carme Bracke and Dr Ignacio Grafia. The authors review preclinical and clinical studies that have explored the use of cells modified with CAR receptors to target fungal, viral and some bacterial infections.
This type of therapy modifies immune cells so that they can identify a specific target and act against it. In oncology, it is mainly used with T lymphocytes, known as CAR-T cells. Researchers are now investigating whether the same principle can be used to enable immune cells to recognise microorganisms responsible for severe infections.
Fungal infections can have a mortality rate of up to 50% in high-risk patients
Invasive fungal infections pose a particularly serious problem for people with weakened immune systems, such as patients with haematological cancers or people who have received a transplant. Even with current antifungal treatments, mortality in high-risk populations often exceeds 40% or 50%. According to the authors, this is compounded by the emergence of fungi that are resistant to available drugs, making these infections even more difficult to treat.
This is where CAR-T therapies could offer a different strategy. Given that these infections occur in patients with severely weakened immune systems, the idea is to directly infuse immune cells that specifically target the pathogens in a similar way to how the immune system would respond in a healthy person. “In these patients, the main problem is not only the infection itself, but also the lack of an effective immune response to control it. CAR-T therapies could make it possible to restore this lost immune function in a targeted way. The studies reviewed have tested different types of modified cells, including T lymphocytes, NK cells and macrophages”, explains Dr Puerta.
The results are particularly promising against Aspergillus spp. and Candida spp. In experimental models, several CAR-T strategies have been able to recognise fungal structures, increase antifungal activity, reduce infection burden and improve survival in animal models. Some approaches have also shown promising results in models of infection with Cryptococcus spp. and Fusarium spp.
A promising strategy that has yet to demonstrate its full potential
The potential of CAR-T therapies in infectious diseases is not limited to fungal infections. The review includes studies on HIV, cytomegalovirus, Epstein-Barr virus, hepatitis B and C, and SARS-CoV-2. At the same time, their potential use against certain bacterial infections has also begun to be explored.
In fact, in the case of HIV, clinical studies using different generations of CAR-T cells already exist. Some strategies have succeeded in reducing the viral reservoir, although they have not yet enabled definitive control of the virus after antiretroviral treatment is discontinued.
In this respect, despite the initial results, CAR-T therapies for infections are still a long way from being incorporated into routine clinical practice. According to the researchers, their safety in patients with active infections therefore needs to be studied further, as does which patients could benefit from them. Selecting the appropriate target is also a challenge, as microorganisms may differ between species or modify the structures that CAR-T cells need to recognise.
The authors suggest that the first applications could focus on patients with severe infections that do not respond to standard treatments or are resistant to multiple drugs, particularly when the available therapeutic options are limited. Future clinical studies will need to determine whether this technology can move from being an experimental strategy to becoming a new tool against some of the most difficult infections to treat.
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