Different therapeutic effects of modified oncolytic viruses
Using oncolytic viruses is a new strategy for cancer immunotherapy. To enhance the therapeutic effect the viruses can be modified with immunostimulatory factors. A study from IGP shows that the effect of such factors depends on the kind of oncolytic virus that is modified. To achieve the desired therapeutic benefits, careful consideration is therefore needed when choosing the virus. The study has been published in the journal Molecular Therapy Oncolytics.
A new method to treat cancer is to use oncolytic viruses. These are viruses that infect cancer cells where they replicate until the cancer cells burst and release new virus particles, that in turn can infect other cancer cells. When the cancer cells are destroyed this elicits an anti-tumour immune response, which contributes to the anti-tumour effect of the oncolytic virus.
Currently, several types of oncolytic viruses are developed for cancer therapy. In the present study, the researchers studied if the anti-tumour effect could be enhanced by arming the viruses with proteins that should stimulate the immune response. The results showed that distinct immune stimulation profiles are elicited when the same immunostimulatory factor is present in different oncolytic viruses.
“We armed two types of oncolytic viruses – vaccinia virus and Semliki Forest virus – with two immune activating proteins and studied the effect in a mouse model of the tumour type neuroblastoma. For the vaccinia virus the presence of the proteins resulted in an enhanced anti-tumour effect through the production of antibodies against the cancer cells. When we used the same proteins in the Semliki Forest virus, instead an immunological response against the virus was induced,” says Di Yu, who has led the study.
The study shows that careful consideration and detailed characterisation are needed when engineering oncolytic viruses with immune-modulators. In the case of Semliki Forest virus, which is very immunogenic by nature, the focus of engineering can be directed towards improving the virus’ ability to burst the cancer cells, inducing a direct viral lytic response. For vaccinia viruses, which by nature have immunosuppressive properties, the focus can be directed towards arming the virus with immune modulators to improve immune response against the cancer cells.
“Our conclusion is that if you want to engineer oncolytic viruses with immune modulating agents you should base the strategy both on the selected virus and on the targeted tumour type, to achieve the desired therapeutic benefits,” says Di Yu.
Y chromosome loss causes heart failure and death from cardiovascular disease
Loss of the Y chromosome in blood cells of men is associated with disease and mortality, but no clear causal relationship has previously been identified. Now, researchers from IGP show in an international study in the journal Science that loss of the Y chromosome in white blood cells causes development of fibrosis in the heart, impaired heart function and death from cardiovascular diseases in men.
Alternative promising approach for sensitive protein detection
Researchers at IGP have developed a new method to detect proteins with high specificity and sensitivity that could be use in future diagnostic analyses of patient samples.
Oral contraceptives and hormone treatment increase stroke risk
A new study from IGP show that oral contraceptives and also hormone replacement therapy at menopause increase the risk of stroke. The increased risk was largest during the first year of treatment, after which it declined. The study, which is now published in the journal Stroke, is based on data from more than a quarter of a million women from the database UK Biobank.
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.