- Chimeric antigen receptor (CAR) T cells are a type of immune cell that have been modified to specifically target certain proteins.
- CAR T cell therapy involves “reprogramming” a person’s own immune cells to fight blood cancers. Currently, approved CAR T cell therapies are designed to attack proteins found in cancer cells.
- Now, a preclinical study from researchers at the Perelman School of Medicine at the University of Pennsylvania suggests that CAR T cell therapy may also improve the outcomes of surgical treatment for solid tumors.
In a new study published in the journal Science Advances, researchers used a unique gel containing human CAR T cells on the surgical wounds of mice after partial removal of the tumor.
The scientists reported that in nearly all instances, the CAR T cells effectively destroyed the remaining cancer cells, enabling the mice to survive when otherwise they would have died due to the return of the tumor.
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Surgery can be an effective cure for solid tumor cancers that have not spread. However, it can be challenging for surgeons to determine where the tumor ends and healthy tissue begins.
As a result, many types of cancer can recur after surgery due to remaining microscopic tumor cells.
To address this issue, the researchers tested a new approach that involves applying anti-tumor treatment to the remaining tissue margins right after the tumor is removed to eliminate any leftover cancer cells.
Targeting solid tumors with CAR T treatments has proven to be more challenging, partly due to the size of the tumors and the ways in which they protect themselves from the immune system.
In this study, the researchers applied this same technique to two other types of cancer that are difficult to treat: triple-negative breast cancer (which is devoid of the three main markers of breast cancer) and human pancreatic ductal carcinoma (the most prevalent form of pancreatic cancer).
Dr. Michael Hurwitz, an oncologist at the Yale Cancer Center and associate professor of internal medicine at the Yale School of Medicine in Connecticut who was not involved in the research, told Medical News Today that “this is a really interesting study about a novel way to prevent cancers from coming back after a cancer has been removed by surgery. The idea is to infuse immune cells that have been engineered to recognize a protein on the surface of the cancer cells and kill them in order to destroy any residual tumor cells that might be left over after surgery.”
The researchers implanted tumors in mice that produce a protein called mesothelin. They then removed the tumors but left some behind, and implanted CAR-T cells that recognize mesothelin in some mice and CAR-T cells that recognize a different protein in others. The results showed that the mice that received anti-mesothelin CAR-T cells were cured, while the others were not, demonstrating the ability of the implanted cells to destroy the remaining tumor cells by recognizing the tumor.
Dr. Michael Hurwitz
Hurwitz explained that “this only worked well when the CAR-T cells were implanted in something called fibrin glue, which kept the cells at the site of the tumor removal (so they wouldn’t diffuse away).”
Dr. Parvin Peddi, a medical oncologist and associate professor of medical oncology at the Saint John’s Cancer Institute in California who also not involved in this research, told MNT that “while it’s an early study in mice, these are intriguing results.”
“CAR T therapy is a form of immunotherapy. It has been approved for some patients with lymphoma and leukemia, but it has not yet been tested for patients with so-called “solid” cancers such as breast or pancreatic cancer. It can be toxic and requires careful monitoring, often in a hospital setting,” Peddi said.
Hurwitz explained that “this study would be considered a ‘proof of concept’ study.”
“That means that the study is really about showing that in theory, certain types of approaches to treatment might be possible,” he explained. “Developing this technology could lead to treatments someday that will make the likelihood of curing peoples’ cancers with surgery much higher.”
Saul Priceman, Ph.D., an associate professor at The City of Hope, a former recipient of an NCCN Foundation Young Investigator Award for research on the use of CAR T therapy in prostate cancer who was also not involved in the research, told MNT that “we know in many cases, surgery does not provide long term curative responses in patients with local but aggressive disease. This study broadens the potential for CAR T cell therapies using fibrin gels in targeting local disease in conjunction with primary cancer treatment options including surgery for more durable outcomes.”
This study further validates the potential for CAR T cells to be pushed to front-line treatment for early-stage diseases that have high recurrence rates following primary treatment (i.e. surgery), including head and neck, prostate, breast, pancreatic and ovarian cancers.
“The study also potentially addresses limitations of CAR T cells in terms of on-target and off-tumor toxicities with localized cell delivery using fibrin gels, such that patients may have improved safety profiles with this treatment with enhanced therapeutic responses,” Priceman explained.
The promising outcomes of this research have prompted researchers at the Perelman School of Medicine to plan a clinical trial for people with locally advanced breast cancer.
“I look forward to a study of CAR T cell therapy in humans in the setting of a clinical trial,” Peddi said.