Sci Transl Med: Is the lysovirus "strong combination" with CAR T therapy that promises to cure solid tumors?

The embedded antigen-liker (CAR) T-cells have been modified to identify specific antigens on tumor cells.
, naturally occurring antigens provide effective targets, such as B-cell antigen CD19.
, however, there are no uniform antigens in tumor cells, which greatly reduces the anti-tumor effect of CAR T therapy.
September 2nd, researchers at Hope City National Medical Center in the United States genetically engineered a lysolytic virus that carries the CD19t gene, which forces tumor cells to express CD19t on the surface for use in targeting CD19-CAR T cells.
the tumor cells that are killed also release the virus, which spreads CD19t to neighboring tumor cells.
results were published in Science Translational Medicine.
specifically, the researchers first created a lysolytic virus (OV19t) to enter tumor cells and begin to produce a truncated CD19 (CD19t).
results showed that three negative breast cancer cells, pancreatic cancer cells, prostate cancer cells, ovarian cancer cells, head and neck cancer cells and glioma cells are rich in CD19t.
after the OV effectively delivered CD19t in-body to solid tumor cells, the researchers looked at whether human CD19t could be transmitted to tumor cells through OV-activated CD19-CAR T cells.
results showed that the lysovirus was able to transmit the antigen, CD19t, to the tumor and induce anti-tumor activity mediated by CD19-CAR T cells.
, in two human heterogeneity transplant tumor models, the combined treatment of OV19t and CD19-CAR T cells led to a significant subsidy of the tumor.
, this combination can also achieve a combination of OV19t and CD19-CAR T cells in immune rat systems.
, about 60 per cent of mice treated with OVm19t and mCD19-CAR T cells in the tumor achieved complete retreat. further analysis of the anti-tumor efficacy of
OVm19t and mCD19-CAR T cells in immunological mouse tumor models showed that CD19-CAR T cell-mediated tumor killing also induced dying tumor cells to release the virus, thus transmitting CD19t tumor expression.
, cancer mice cured with a combination of lysovirus and CAR T cells showed an increase in protective anti-tumor immunity.
suggests that the immune system has established a memory response to the tumor.
OVm19t tumor immersion CD19-CAR T cell therapy for endogenated T cells and metastatic mCD19-CAR T cells has been approved by the FDA for the treatment of B-cell lymphoma and acute lymphoblastic leukemia.
new study may expand the use of CD19-CAR T cells in treating patients with solid tumors.
, researchers are designing a clinical trial to test patients for this combination.
the trial will first test the safety of OV19t in solid tumor patients, and if it is found to be safe and effective, lysovirus and CAR T cell therapy can be detected in turn.
the trial is expected to begin in 2022.
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