immunotherapy

CAR-T cells, T lymphocytes modified in the laboratory to attack tumor cells, have shown promise against certain types of cancer. Now, a US team has followed the same concept and introduced artificial receptors into astrocytes, a type of nerve cell, with the aim of reducing the amyloid plaques characteristic of Alzheimer's disease. The experiments, conducted in mice, showed a significant reduction in amyloid, although no changes in the animals' behavior were observed. The results are published in Science. 

Cancer patients receiving a type of immunotherapy known as Immune Checkpoint Inhibitor (ICI) have a higher risk of serious adverse events, such as aortic aneurysm rupture, interstitial lung disease, myositis and liver failure, according to a study published in PNAS. "Establishing formal contraindications for ICI users seems warranted," concludes the analysis, based on more than 290,000 cases from pharmacovigilance databases of the US Food and Drug Administration and the World Health Organisation.

Although CAR-T cells have been effective against certain blood cancers, they have not worked well in solid tumors due to the lack of a common target on the surface of the cells. A study published today in the journal Science has developed ultra-sensitive CAR-T cells capable of detecting even very low levels of the CD70 protein, a promising target. The researchers succeeded in eradicating kidney, ovarian, and pancreatic tumors in preclinical models.

A phase 3 clinical trial conducted in China tested 210 patients with advanced non-small cell lung cancer—the most common type—to see whether the time of day when immunotherapy and chemotherapy were administered influenced their effectiveness. The data indicate that, on average, those who received therapy after 3 p.m. did not see their cancer worsen for 5.4 months. In contrast, those who received it before that time did not see their cancer worsen for an average of 11.7 months, almost twice as long. Overall, response rates were 56.2% and 69.5%, respectively. The results, published in Nature Medicine, suggest that scheduling therapy early in the day may offer a simple and cost-free way to improve treatment efficacy.

Over the past 20 years, a class of cancer drugs known as CD40 agonist antibodies has shown great potential, but also limited impact in patients and adverse reactions. In 2018, it was demonstrated that they could be improved to boost their effectiveness and limit serious side effects. A study published in Cancer Cell reports the results of using one of these drugs in a small phase 1 clinical trial: out of 12 patients, all with different types of metastatic cancer, six saw their tumors shrink, including two in whom they disappeared completely.

Certain immunotherapy treatments for cancer work by releasing the brakes on our defences. However, their response varies and is not uniform in all patients. A team in the United States has now published a study in Nature according to which certain autoantibodies present in patients could improve the efficacy of the therapy, which would explain some of this variability and could be used to design future complementary treatments.

A phase 1 clinical trial has tested the safety and preliminary efficacy of a new form of CAR-T cell therapy - which they call “armed” - in patients with lymphoma. The novelty consists of adding another gene to help increase response. Of the 21 patients treated, all resistant to multiple lines of treatment including approved CAR-T therapies in 20 of them, 81% showed a response and 52% went on to achieve complete remission without significantly greater side effects than with the standard option. The results are published in the journal NEJM.  

In mice, a therapy based on editing regulatory T-cells can suppress an immune reaction against gluten, according to a study in Science Translational Medicine. Studies in animals with coeliac disease would be needed to assess the efficacy of this cell therapy in restoring gluten tolerance, the authors say. 

An international team has found that aspirin is capable of reducing the appearance of metastasis in mice, by enabling the activation of T lymphocytes capable of recognising tumour cells. The research showed that several different mouse cancer models — including breast cancer, colon cancer and melanoma — treated with aspirin showed a lower rate of metastasis in other organs, such as the lungs and liver, compared to untreated mice. According to the authors, who publish the results in the journal Nature, ‘the finding paves the way for the use of more effective anti-metastatic immunotherapies’.

A team of US researchers has followed some patients treated with CAR-T therapies in a small clinical trial conducted between 2004 and 2009 to treat children with neuroblastoma, a nerve cell tumor that can have a poor prognosis. At least one of them, a woman who was treated with CAR-T as a child, remains in remission 18 years later, the longest duration of such therapy described to date. The results are published in the journal Nature Medicine.