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Therapies for aggressive, recurrent glioblastomas are sorely needed but frequently fail in trials. A first-in-human trial of CAN-3110, an engineered herpes simplex virus 1 (HSV1), shows that it is safe and seems to extend survival and stimulate immune responses — particularly in people with antibodies to HSV1.
The protein netrin-1 is involved in embryonic development and is upregulated in various cancers, including endometrial cancer. In mouse models and a first-in-human trial, blocking netrin-1 with a humanized monoclonal antibody, NP137, prevents a cellular change called the epithelial–mesenchymal transition and inhibits tumour growth.
Individuals with limited English proficiency were less likely to participate in, and sign consent documents in their primary language for, clinical trials led by academia than those led by industry. This retrospective analysis shows that inadequate funding for translation is a barrier to equitable trial enrolment and appropriate informed consent in academic trials.
Researchers have developed a system to classify genetic mutations that could be addressed by therapeutic interventions that use ‘splice-switching antisense oligonucleotides’. This framework identified multiple eligible mutations among 235 people with the genetic disorder ataxia–telangiectasia. An oligonucleotide that was specific to one of these mutations was advanced to a proof-of-concept individualized trial.
Spinal-cord injury interrupts communication between the brain and spinal cord, leading to paralysis. An implant that decodes the brain signals that control movements and drives electrical stimulation of the spinal cord re-establishes this communication, enabling an individual with spinal-cord injury to walk naturally.
Leukaemias characterized by the rearrangement of the gene KMT2A or mutation of the NPM1 gene depend on the protein menin. In a first-in-human trial, the menin inhibitor revumenib had minimal severe adverse effects and showed promising clinical activity in individuals with these types of leukaemia.
Immune-related adverse events are a limiting factor in the use of cancer immunotherapies but the mechanisms and risk factors are largely unknown. T cells that recognize a heart-muscle protein mediate an immunotherapy-related condition called myocarditis.
Treatment with the drugs relatlimab and nivolumab before the surgical removal of a type of cancer called melanoma resulted in tumours becoming inviable in 57% of individuals, and no severe adverse effects were observed. People with a favourable treatment response had a better survival outcome than did those who did not respond.
For breast cancers that have spread, a randomized phase II clinical trial shows that using genomic analysis to target therapies can improve outcomes, but only in people with a genetic alteration that has previously been associated with antitumour activity in clinical trials.
An improved approach has been developed for producing precisely designed immune cells called CAR T cells that recognize and kill cancer cells. CAR T cells generated in this way were safe and showed potential therapeutic effects in individuals with a relapsed or treatment-resistant form of the immune-cell cancer called B-cell non-Hodgkin’s lymphoma.
