Science Sub-Journal: Using viral simulation drugs to help the immune system target and kill cunning cancer cells

OCT 23, 2020 /--- In a new study, researchers at the University of California, Los Angeles, found that a drug that activates the body's natural defense system like a virus may also make certain invisible melanomas visible to the immune system, making immunotherapy better targeting them.
these findings offer the possibility of using drugs that simulate the virus to overcome immunotherapy resistance to tumors with interferon signaling defects and help develop more personalized treatments for cancer patients who are difficult to treat.
study was recently published in the Journal of Science Translational Medicine under the title "Uncoupling interferon signaling and antigen presentation to overcome to overcometherapy resistance due to JAK1 loss in melanoma".
photo from Science Translational Medicine, 2020, doi:10.1126/scitranslmed.abb0152.
immunotherapy relies on T-cells' ability to recognize and kill tumor cells," said Dr. Anusha Kalbasi, co-author of the paper and an assistant professor of radiation oncology at the University of California, Los Angeles School of Medicine.
, in some patients, tumors evade the immune system by mutated genes involved in interferon signaling path pathlines.
this is a key path, because it usually allows the tumor to increase its antigen delivery, an intricate mechanism that makes the tumor visible to T cells.
" interferon is a protein in cells that responds to viral infections by blocking the virus's ability to replicate and alerting the immune system to it.
the interferon signals in the tumor helps slow tumor division and can lead to the release of more immune cells into the tumor.
, "This coordinated effort to transduct interferon signals can help the immune system better identify and kill tumor cells," kalbasi said.
" the researchers first tried to overcome interferon signaling defects by using step-T-cell therapy, an immunotherapy that involves extracting T-cells from patients and genetically adapting them in the lab to identify and kill cancer cells.
they found that these T-cells were still ineffective against tumors with interferon signaling defects.
the researchers then genetically modified melanoma cells in mice using a gene called NLRC5.
NLRC5 increases antigen delivery and restores the effectiveness of T-cells even without interferon signal transduction.
this method is effective in mice, genetic modification of tumor cells in humans is not so simple.
Kalbasi and his colleagues turned to a virus-simulation drug called BO-112, which activates the pathway of viral perception in tumors.
when the drug was injected directly into the tumor in the lab, they found that activation of the virus-sensing pathway increased antigen delivery even when interferon signals were defective.
, these tumors can be identified and killed by T-cells. "This study helps us understand the interdependence between interferon signaling and antigen delivery, which gives us an important understanding of how tumor cells are recognized by the immune system," said lead author Dr. Antoni Ribas, a professor of medicine at the University of California, Los Angeles School of Medicine and lead author of the
paper.
strategies to promote antigen delivery make tumors more visible to the immune system, which will make immunotherapy effective for more tumor types.
also highlight the potential of other promising clinical approaches that bypass tumor interferon signaling and antigen delivery, such as CAR-T cell therapy.
CAR-T cells can recognize and kill tumor cells even when there is no antigen delivery.
Kalbasi is now leading a human clinical trial in which immuno-checkpoint blocking drugs nivolumab and BO-112 are treated in patients with certain types of sarcoma who undergo radiation after surgery.
idea is to activate the immune system to fight tumors in patients while they are still in the body.
(bioon.com) Reference: 1.Anusha Kalbasi et al. Uncoupling interferon signalling and antigen presentation to overcometherapy resistance due to JAK1 loss in melanoma. Science Translational Medicine, 2020, doi:10.1126/scitranslmed.abb0152.2.Virus-mimicking drug helps immune system target cancer cells