Scanning Electron Micrograph of Pancreatic Cancer Cells
Anne Weston, EM STP, Francis Crick Institute/Science Photo Library
In a groundbreaking clinical trial in the United States, researchers have found that a novel viral treatment halted the progression of pancreatic cancer in three patients. While further assessments in larger trials are necessary, these early results are promising, particularly given that only minimal quantities of the virus were administered during initial safety tests.
According to Masato Yamamoto, who spearheaded the research at the University of Minnesota, “The efficacy exceeded our expectations, particularly considering we injected merely one-tenth of the targeted dose for pancreatic cancer.”
Pancreatic cancer is notoriously known as one of the deadliest cancers. This is due in part to the fact that symptoms often emerge late, when the cancer has typically advanced beyond the point of surgical removal. For patients diagnosed with this illness, the prognosis is grim: they usually survive for only about 3 to 6 months.
The stiffness of pancreatic tumors presents another significant challenge, inhibiting chemotherapy drugs from penetrating effectively. As Dr. Yamamoto aptly notes, “Pancreatic tumors are as hard as a hockey puck.” Additionally, these tumors can evade detection by the immune system, rendering immunotherapy treatments that boost immune activity against cancer cells largely ineffective.
One of the trial participants had a pancreatic tumor measuring 7 centimeters in diameter and underwent treatment about a year ago, with the other two patients treated subsequently. Fortunately, their tumors have not grown since treatment began. “They are all alive and exhibit clinically stable disease,” Dr. Yamamoto shared at the Annual Meeting of the American Society for Gene and Cell Therapy held earlier this month in Boston, Massachusetts. An additional 15 patients are now set to receive higher doses to determine the optimal treatment level.
Dr. Kai Brown, a pancreatic surgeon at the Royal North Shore Hospital in Sydney, cautioned, “While this shows intriguing early promise, we must maintain a cautious optimism. The history of oncology is riddled with initially encouraging signals that have vanished by the time rigorous phase III [late-stage] testing was completed. Thus, these initial results ought to be viewed as hypothesis-generating.” Notably, the trial currently lacks a control group, making it difficult to ascertain if the cancer-killing virus is more effective than existing treatments.
The virus being tested is a genetically modified adenovirus designed to proliferate specifically within tumors while avoiding healthy tissues. Its replication is activated by cyclooxygenase 2 (COX-2), an enzyme found in much higher levels in cancer cells than in normal cells. Upon infecting cancer cells, the virus can rupture and lead to their death, thereby releasing more virus to infect adjacent cancer cells.
During this trial, the virus was injected directly into the tumor via a thin tube guided down the patient’s throat, reaching the pancreas. An ultrasound probe at the tube’s end assisted in visualizing the tumor’s location.
Dr. Yamamoto speculated that the tumor’s growth has halted without regression likely due to the low treatment dosage. He believes that as the virus replicates, the number of infected tumor cells may diminish over time.
As tumor cells begin to break apart, the immune system may identify the cancer and initiate its attack. “The patient’s immune system may recognize that something is wrong and start targeting the tumor,” he explained. If successful, this treatment could potentially combat metastatic pancreatic cancer as well.
To enhance this innate immune response, Yamamoto and his team plan to combine viral therapies with immunotherapies, including checkpoint inhibitors—drugs that block proteins preventing the immune system from attacking cancer cells—in future clinical studies.
Historically, adenoviruses have caused cold and flu-like symptoms in their unmodified form, but they have shown promise as cancer treatments. In the 1950s, for example, women with cervical cancer were treated with unmodified adenovirus, witnessing some success in clinical trials. However, safety and efficacy issues highlighted the need for genetic engineering to tailor adenoviruses to specifically target cancer cells.
The only FDA-approved cancer-killing virus, T-VEC, is a genetically modified herpes simplex virus injected directly into melanoma tumors, inducing cell rupture and death.
Topics:
Source: www.newscientist.com
