Boosting Immunotherapy In Breast Cancer Patients

The T cell response of the immune system can be effectively boosted to attack solid tumors like breast cancers by adding a small molecule to a treatment procedure called chimeric antigen receptor-T (CAR-T) cell therapy which helps recruit more immune cells at the tumor site.

The study conducted by researchers at the UNC Lineberger Comprehensive Cancer Center is published in the Journal of Experimental Medicine.

‘For the treatment of breast cancer, addition of two small molecules called the stimulator of interferon genes (STING) agonists DMXAA and cGAMP to chimeric antigen receptor-T (CAR-T) cell therapy can decrease tumor growth and increase survival in patients.’

For the treatment of patients with B-cell leukemia or lymphoma, CAR-T immunotherapy in which T cells are modified in the laboratory to express chimeric antigen receptors, CARs, target surface proteins on cancer cells. This therapy has shown promising results. The research conducted in mouse models shows that CAR-T therapy can be effectively used against solid tumors as well.

Jonathan S. Serody, MD, the Elizabeth Thomas Professor of Medicine, Microbiology and Immunology and director of the Immunotherapy Program at UNC Lineberger said, "We know that CAR T cells are safe for patients with solid tumors but so far they have not been able to cause significant tumor regression in the overwhelming majority of people treated. Now we may have a new approach to make CAR T cells work in solid tumors, which we think could be a game-changer for therapies aimed at an appreciable number of cancers."

In CAR-T cell therapy the T cells infused back into the patients have to migrate to the tumor site. For treatment of non-solid tumors like lymphomas, CAR-T cells move in the bone marrow and other organs that make up the lymphatic system. However, for solid tumors like breast cancer, even if they are able to migrate to the tumors, they do not persist and expand well there due to the nature of the microenvironment surrounding such tumors.

The researchers studied ways to direct the lab-expanded cells toward the site of solid tumors by mainly focusing on Th17 and Tc17 cells, which have better survival capabilities as they persist for a long time in the micro-environment surrounding the tumor.

To increase the level of Th17 and Tc17 cells near solid tumors, they turned to two small molecules that can activate an immune response: the stimulator of interferon genes (STING) agonists DMXAA and cGAMP.

Although DMXAA worked well in mouse studies, in human clinical trials it was not able to activate human STING. However, the other STING agonist cGAMP, was able to activate human STING and is known to boost the human immune system.

When researchers injected mice with cGAMP, increase in proliferation of T cells and those cells were able to migrate to the tumor site. The end result showed a significant decrease in tumor growth and enhanced survival.

Serody said, "We hope to be able to study cGAMP in humans fairly soon. We will look to see if we can produce improvements in the treatment of head and neck cancers first, and if that proves promising, move into other forms of cancer by using CAR T cells generated by one of our colleagues here at UNC."

Source: Medindia