Manel Juan

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an aggressive tumor that is often diagnosed at advanced stages. Some people are at high risk of developing it due to a hereditary predisposition (10% of cases) or an injury. A new Phase 1 clinical trial has tested, in high-risk patients, a vaccine targeting several mutations in the KRAS gene responsible for more than 90% of these tumors. The vaccine has been shown to be safe and has stimulated specific immune responses, detectable in the blood up to two years later, in 90% of the study participants. The study is published in Cancer Discovery.

An international team has published the five-year follow-up results of a phase 2b clinical trial testing a personalised cancer vaccine in combination with standard immunotherapy treatment for melanoma. After this period, the probability of cancer recurrence was around 50% lower in the group of patients who received the vaccine. Furthermore, the probability of metastasis was almost 60% lower. The results are being presented at the ASCO (American Society of Clinical Oncology) conference and published in the Journal of Clinical Oncology.

For the first time, CAR-T cell therapy has been used to treat a patient with three different autoimmune diseases – autoimmune haemolytic anaemia, immune thrombocytopenia and antiphospholipid syndrome – which were life-threatening and had resisted years of treatment. The patient, who previously required daily blood transfusions, has been in remission for a year without the need for further treatment since then. The case report, published in the journal Med, suggests that these therapies may help treat complex and severe autoimmune diseases. 

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.  

According to a new study published in Science, a machine learning-based artificial intelligence (AI) system - called Mal-ID - can decipher an individual's history of infections and diseases in the immune system. The authors say this provides a powerful tool with the potential to accurately diagnose autoimmune disorders, viral infections and vaccine responses.

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. 

The Karolinska Institute has awarded the Nobel Prize in Medicine or Physiology to Katalin Karikó and Drew Weissman for their groundbreaking discoveries, which have radically changed our understanding of how mRNA interacts with our immune system, and made it possible to develop vaccines at unprecedented speed during the covid-19 pandemic.