Science sub-journal cover: lysovirus and CAR-T cells work together to eradicate solid tumors

In a recent research paper published in the scientific journal Translation Scienceal Medicine, scientists at the City of Hope National Medical Center in the United States have made significant progress by combining two powerful immunotherapy therapies, lysovirus and car-embedded antigen-treated (CAR) T-cell therapy, to target solid tumors that would otherwise be difficult to treat alone with CAR-T therapy.
new study is expected to expand the treatment of CAR-T cells to patients with a variety of solid tumors.
" our study shows that lysovirus is a powerful way to target solid tumors more effectively in combination with CAR-T cell therapy.
Saul Priceman, one of the authors of the study, said: "This treatment platform addresses two major challenges that make it difficult to treat solid tumors with immunotherapy.
first, solid tumors, suitable for T-cells with CAR redirect targets are limited.
Second, solid tumors are surrounded by the micro-environment of so-called immunosuppressive tumors, a barrier that prevents a CAR-T cell from functioning effectively when it tries to enter the tumor, survive and kill cancer cells.
lysolysed tumor virus can break through this barrier.
" study is also used as a cover story for Science Translational Medicine (Photo: Science Translational Medicine; Credit: A. K. PARK, S.I. IN this preclinical study, scientists skillfully equipped CAR-T cells with "drivers" to enter solid tumors using the lysovirus.
they genetically engineered a lysolytic virus to enter tumor cells, forcing them to express a cut-off CD19 (CD19t) on the surface.
trials have shown that the lysolytic virus, known as OV19t, can work in triple-negative breast cancer cell lineages as well as in pancreatic, prostate, ovarian and head and neck cancer, and brain tumor cells.
-modified lysovirus allows tumor cells to express CD19 (purple) on the surface (Photo: References. ; Credit: City of Hope) After tumor cells infected with OV19t, scientists used CAR-T cells specifically targeted at CD19 to identify and attack these solid tumors.
tests conducted in in-body experiments and various mouse tumor models showed that CD19t was expressed in tumor cells much faster than viruses killed them, creating a time window for CAR-T cells targeting CD19.
that were killed by the virus released additional copies of the virus and spread to neighboring tumor cells, making them targets for CAR-T cells.
, the combination of lysovirus and CAR-T cells creates a powerful synergistic effect.
, after using this combination therapy to eradicate solid tumors, mice showed long-term protective anti-tumor immunity, and the immune system established a memory response to tumors.
this result means that this combined treatment will help prevent recurrence.
researchers say they are now designing clinical trials to test the combination in patients.
of course they will first test the safety of OV19t in solid tumor patients.
if proven to be safe and effective, lysovirus and CAR-T cell therapy can be tested in turn.
is expected to begin in 2022.
resources: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effective group immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors, DOI: 10.1126/scitranslmed.aaz1863