In a recent study entitled “T Cells Engineered against a Native Antigen Can Surmount Immunologic and Physical Barriers to Treat Pancreatic Ductal Adenocarcinoma,” scientists discovered that a newly designed immunotherapy – T cells targeting a protein called mesothelin – is capable of rescuing survival in more than 75 percent of mice with pancreatic cancer.
Pancreatic cancer is fatal in the majority of cases as a result of pancreatic tumor cells’ ability to recruit and build a protective physical barrier that shields tumors from the cytotoxic action of the immune system. Additionally, pancreatic tumors’ resilience is especially high when compared to other tumors, and are capable of growing and thriving with limited blood supply. Since chemotherapy reaches tumors via blood circulation, pancreatic tumors are also more protected from the damages chemotherapy inflicts upon tumor cells.
In this study, scientists led by Drs. Sunil Hingorani and Phil Greenberg at the Fred Hutchinson Cancer Research Center engineered T cells (key cells of the immune system) to recognize and kill cells expressing a protein called mesothelin – a protein previously reported to be expressed by all pancreatic tumors. The team discovered that mesothelin-targeted T cells travel into the tumor where they infiltrate and induce tumor cell lysis.
Ingunn Stromnes, a research associate in Greenberg and Hingorani’s labs and study first author commented in a press release, “Everything up until now indicated that T cells can’t get into these tumors. All we may really need is the right kind of T cell to actually have a major impact.”
The team used a mouse model for human pancreatic cancer, which is actually slightly more aggressive when compared to the human cancer. They showed that mice receiving mesothelin-targeted T cells lived on average 96 days (after the cancer became detectable), while control mice (receiving T cells engineered to recognize a non-cancerous protein) survived 54 days. Therapy with mesothelin-directed cells resulted in an increased survival of 78 percent.
Now, researchers are fine-tuning the therapy in mice but have already designed a human version of mesothelin-targeted T cells, and is planning to launch the first phase 1 clinical trial to test the safety of the therapy in patients with advanced pancreatic cancer.
Greenberg noted, “As best we can tell, this would be a better therapy than anything that exists for pancreatic cancer right now. It’s hard to be this optimistic without ever having treated a pancreatic cancer patient with this [therapy], but the biology of what we’re doing looks so good.”
Hingorani added, “We’ve tested other approaches that might have translated to a 10 percent or 20 percent increase in survival, which is still significant in this disease. There have been lesser improvements that have been FDA-approved, but that’s not what drives us. There isn’t enough time in my lifetime to keep doing 10 percent increments if we want to dramatically alter the prognosis for this disease.”
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