CAR-T therapy's new partner, STING astrists

Source: Medical Rubik's Cube Pro CAR-T therapies like Novarma's Kymriah and Gilead's Yescarta have changed the fortunes of some leukemia and lymphoma patients, but how to apply this technique to physical tumors is a challenge.
Immune pathline, known as interferon gene stimulator (stimulator of interferon genes, STING), has long attracted the attention of the cancer community and has attracted the interest of large pharmaceutical companies because activating it creates an inflammatory environment that increases the ability of immune cells to attack cancer.
in clinical trials, the results of experimental therapies that activate STING have been mixed.
is investigating a combination therapy between PD-1 inhibitor Keytruda and STING agonist MK-1454, the pharmaceutical giant's initial attempt to use MK-1454 as a monotherapy for solid tumors with little effect.
developed a STING agitant (ADU-S100) in partnership withaduro Biotech, but removed the ADU-S100 from its portfolio in 2019 due to disappointing clinical results.
, however, has not dented industry interest in STING, with a number of companies and institutions still developing STING targeted therapies.
A recent study by the University of North Carolina's Lineberger Comprehensive Cancer Center showed that adding STING agonists to car-T cell therapy can effectively enhance T-cells' ability to attack solid tumors, such as breast cancer, and help recruit more immune cells to fight tumor sites.
study was published December 31 in the journal Of August Medicine.
We know that CAR-T cells are safe for solid tumor patients, but so far they have not been able to cause significant tumor subsidion in the vast majority of patients treated," said Jonathan S. Serody, professor of microbiology and immunology at Journal of Research Medical, who led the study.
now we may have a new way to make CAR-T cells work in solid tumors.
"For CAR-T cell therapy to be effective, T cells that are returned to the patient must be able to migrate to the tumor site."
when treating non-physical tumors such as lymphoma, CAR-T cells return to the bone marrow and other organs that make up the lymphatic system.
for solid tumors, such as breast cancer, this is usually not the case.
Serody points out that even if they do migrate to the tumor, they do not survive and multiply well there due to the microennity surrounding the tumor.
looking for ways to direct CAR-T to solid tumors, Serody and his colleagues focused on two cells, Th17 and Tc17, which are known to exist in the micro-environment around the tumor.
to promote the build-up of Th17 and TC17 cells near solid tumors, they tried two small molecules that activate the immune response: STING astrist DMXAA and cGAMP.
when CAR-T, which is produced from Th/Tc17 cells, was combined with small molecule STING astrologists, the researchers found that these engineered cells survived long periods of time in tumor microencessions.
using single-cell RNA sequencing, they demonstrated that DMXAA promotes the transport and persistence of CAR-T cells due to the production of a coercion factor environment.
this environment promotes the recruitment of CAR-T cells and the regulation of the micro-environment of immunosuppressive tumors by changing the balance of immunostific and inhibitory myelin cells.
, DMXAA played a very good role in mouse studies, but it did not activate the human STING path.
another STING agitant, cGAMP, does activate the body's STING path, strengthens the body's immune system, and is also effective in mice.
Serody's trial, breast cancer model mice injected with cGAMP showed enhanced proliferation of T-cells, which migrated to the tumor site.
result is a significant reduction in tumor growth and an increase in survival.
, however, the team reported that only PD-1 and GR-1 monoants were added to Th/Tc17 CAR-T cell therapy in combination with STING astrologists to achieve a continuous subsidion of the tumor.
"these data indicate a viable strategy to increase car-T activity in solid tumors, and we hope to be able to study the effects of cGAMP in humans as soon as possible."
we will first look at whether progress can be made in the treatment of head and neck cancer, and if this proves promising, further research will be conducted on the treatment of other forms of cancer.
," Dr. Serody concludes.
: 1 s combined approach can boost breastcancer immunotherapy, study suggests (Source: Medical Press) 2 s NuoXu et al, STING agonist promotes CAR T cell trafficking and persistence inbreast cancer, Journal of Experiment Medicine (2020). DOI:10.1084/jem.20200844 3 s Putthe 'STING' on CAR-T cells to turn turn to them againstst breast cancer and other solidtumors (Source: FIERCE Biotech) 4?points Study of the way to boostimmunotherapyst breast, other solid tumors (Source: Eurek Alert)