Combination of technologies could be used in drug development
A new combination of technologies can be used to examine how drugs interact with their targets. This is shown by IGP researchers in a paper published in the journal Analytical Chemistry. The method can be used to analyse a large number of samples, in particular for small sample sizes, and could be applied during drug development and in the clinic.
The efficacy of drugs depends on how well the compounds can modulate the primary target molecule; a process referred to as target engagement. Similarily, interactions with unintended target proteins can result in toxicity and other adverse effects.
The ability to monitor target engagement in cellular contexts is therefore important during the development of new drugs. In the present study the researchers have studied a new method to do so.
“In the early hit identification phase of drug development an assay called CETSA can be combined with mass spectrometry to reveal drug-target engagement for large sets of proteins. However, the analysis is slow, requires substantial amounts of the sample material and it often misses proteins of specific interest. We have instead combined CETSA with the PEA technique, a variant of proximity assays previously developed in our lab, and found that it worked equally well,” says Rasel Al-Amin, researcher in Ulf Landegren’s group and first author of the paper.
The new combination of methodologies allows analyses of target engagement with large numbers of proteins. This renders the technique suitable when many drug candidates or many samples should be analysed. The approach will be particularly valuable when limited amounts of materials are available. It could potentially also be used for corresponding analyses in routine clinical care.
Rare genetic variants are not the main cause of common diseases
Although some rare variants can significantly increase the risk of disease for a few individuals, the majority of the genetic contribution to common diseases is due to a combination of many common genetic variants with small effects. This is shown by researchers at IGP and other departments at Uppsala University in a new comprehensive study published in the journal Nature Communications.
Subgroups of brain tumours associated with cell origin and disease prognosis
Researchers at IGP have detected different subgroups of the brain tumour form glioblastoma, where the cancer cells’ properties depend on which cell type they originate from. The used analysis method could also separate glioblastoma patients with significant differences in survival. The findings open up for identifying specific therapeutic targets for the new subgroups of glioblastoma.
Armed CAR-T cells to better fight cancer
Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at IGP have now developed armed CAR-T cells that reinforce the immune defence against cancer and that could increase the possibilities to successfully treat solid tumours. The study has been published in the journal Nature BioMedical Engineering.
Inflammation and net-like protein structures in cerebral cavernous malformations
In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers at IGP now show in a new study that white blood cells and protein structures associated with the immune response infiltrate the vessel lesions. The findings support that inflammation has a role in the development of cavernoma and indicate a potential biomarker for the disease.
Protein landscape on cancer cells mapped with new technology
In recent years, great advances have been made in the development of new, successful immunotherapies to treat cancer. Two types of targeted immunotherapies that have revolutionised areas of cancer care are CAR T-cell therapy and antibody treatments. However, there are still significant challenges in the identification of cancer cell surface proteins that function as targets for immunotherapies. Mattias Belting, professor at Lund University and senior consultant at Skåne University Hospital, and guest professor at IGP, is well on the way and his group’s findings are now published in the journal PNAS.
CRISPR-Cas9 can generate unexpected, heritable mutations
CRISPR-Cas9, the “genetic scissors”, creates new potential for curing diseases; but treatments must be reliable. In a new study, researchers have discovered that the method can give rise to unforeseen changes in DNA that can be inherited by the next generation. These scientists therefore urge caution and meticulous validation before using CRISPR-Cas9 for medical purposes.
New technology to study DNA in archived tissue samples
Researchers at IGP have developed a technology that allows studies of DNA profiles in archived tissue samples. The technology permits investigators to better understand regulation of gene activity in cancer and precision medicine.
New genes associated with relapse of acute myeloid leukemia
In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.