Ignacio Melero

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.  

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. 

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. 

A multidisciplinary study involving several Spanish research groups has preclinically tested a new type of immunotherapy for multiple myeloma. Instead of modifying T cells to attack the tumour directly, as CAR-T cells do, they have managed to make them secrete bispecific antibodies, which bind to the tumour on one side and to other T cells on the other, attracting them to the tumour. According to the authors, this cell therapy was more effective than traditional CAR-Ts and could generate less resistance. The results are published in the journal Science Translational Medicine. 

The US Food and Drug Administration (FDA) has issued a statement reporting that it has received reports of T-cell tumours in patients who received various CAR-T cell treatments. As quoted in the statement, "although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action".

A team of scientists led by the University Hospital Zurich (Switzerland) has tested a new treatment for glioblastoma, a highly aggressive nervous system tumour with a poor prognosis. The therapy consists of a fusion protein that combines the TNF factor - a key factor in the processes of inflammation and immune response - with an antibody that targets the tumour matrix. The researchers, whose results are published in the journal Science Translational Medicine, have studied its action together with a type of chemotherapy both in mice and in six patients included in a phase 1 clinical trial.