Additive boosting of immune system T cells to efficiently attack solid tumors, such as breast cancer, can be achieved by adding a small molecule to a treatment technique called chimeric antigen receptor T cell therapy.
The boost helps to boost the amount of immune cells that can respond to cancer.
The results are being published today (December 31, 2020), in the Journal of Experimental Medicine.
CAR-T immunotherapy, in which T cells are changed in the lab to express chimeric antigen receptors (CARs) that in turn target surface proteins on cancer cells, has had promising results in the treatment of B-cell leukemia or lymphoma.
Moreover, there are expectations that the use of CAR-T therapy can boost treatment of solid tumors as well.
“We know that CAR-T cells are safe for patients with solid tumors, but until now they have not been able to cause significant tumor regression in the vast majority of individuals treated,” said Jonathan S. Serody, MD, the Elizabeth Thomas Professor of Medicine, Microbiology and Immunology and director of the Immunotherapy Program at UNC Lineberger. “Now we may have a new approach to CAR T cells working in solid tumors, which we think could be a game-changer for therapies targeting a substantial number of cancers.”
The corresponding author is Serody and the first author is Nuo Xu, PhD, formerly a doctoral student at UNC Lineberger and UNC School of Medicine.
To be successful in CAR T cell therapy, the infused T cells must be able to move to the tumors in the patients.
When treating non-solid tumors, such as lymphoma, CAR-T cells travel to the bone marrow and lymphatic system where they clear the body of cells.
Typically, though, it is not of the same vivacity with solid tumors, like breast cancer.
Even if the E-coli could live in the tumor, it would not spread very well in the tumor because of the special microenvironment.
Serody and colleagues investigated how expanding cells in the laboratory could be used to guide them to the location of solid tumors.
The researchers studied Th17 and Tc17 cells, which are known to live longer in the microenvironment surrounding a tumor, in part because of their superior ability to survive there.
To induce Th17 and Tc17 cell aggregation, researchers switched to a pair of small molecules that activate the immune system: the synthetic STING agonists DMXAA and cGAMP.
While DMXAA has worked well in rodent models, it has not been effective in human trials because it does not trigger STING.
In comparison to cGAMP, STING immobilizing agonist is believed to improve the human immune system.
It prevents cancer in mice.
In Stokes’s experiments, mice injected with cGAMP developed more T cells with increased motility, and these migrated to the tumor site.
Effects showed a reduction in tumor size and increased survival.
“We hope to study cGAMP in humans soon,” “We’ll see if we can make improvements in treating head and neck cancer first, and if that proves promising, we’ll move on to other forms of cancer using CAR-T cells generated by one of our colleagues here at UNC.”
UNC Lineberger has a wide array of scientific, technological and clinical capabilities which will contribute to the development and delivery of CAR-T immunotherapy to patients.
The cancer center currently has nine CAR-T clinical trials in progress, and is planning new trials to treat a wide variety of solid tumors.
It also provides patients access to FDA-approved CAR-T therapies.
Source: 31/12/20, The Journal of Experimental Medicine.
The paper’s authors are also Alexander C Robeson, PhD Peishun Shou, PhD Hemamalini Bommiasamy, PhD Sonia J Laurie, PhD Caryn Willis, MS Gianpietro Dotti, MD Benjamin Vincent, MD UNC Lineberger and UNC School of Medicine, Douglas C Palmer, PhD, National Cancer Institute and Nicholas P Restifo, MD, Lyell Immunophar, Inc, formerly of the National Cancer Institute.
This research has been funded by grants from the National Cancer Institute and the President’s Cancer Council.