immunotherapy

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. 

CAR-T cell-based treatments have been successful against some blood tumours, but are much less effective for solid tumours. A phase 1 clinical trial has tested their use in 11 children and young adults with diffuse midline glioma, a tumour of the nervous system that is considered incurable. The results, published in the journal Nature, indicate that the treatment improved functional status in nine of the 11 patients. One of the four who showed a strong response is still healthy four years later.

The regulatory agencies for medicines in the United States and Europe have issued statements informing about a possible risk of developing certain types of tumors following CAR-T cell immunotherapy treatment. What do we know so far? What is the real risk? Does the benefit-risk balance still hold? Has anything changed after these alerts? We answer these questions with expert opinions and the data currently available. 

Cancer immunotherapy, and in particular the so-called checkpoint inhibitors, have improved the prognosis of several types of tumours. However, they are not effective in everyone. Two early-stage clinical trials have tested the addition of a type of immunomodulator to this therapy in patients with lung cancer and Hodgkin's lymphoma, with apparent good results. The results are published in the journal Science.  

CAR-T cell therapies may, in some cases, produce tumours secondary to treatment. A few months ago, the US Food and Drug Administration (FDA) said it was assessing this risk. Now, a study conducted at Stanford University Medical Center (USA) has tracked 724 patients who received this type of treatment since 2016. Of these, 14 developed another blood tumour, but only one was a T-cell lymphoma that could be a direct consequence of the therapy. Further analysis ruled out this link. The results are published in the journal NEJM.