SynergisticAntiTumorWords
--Betting on a Winner—Combination Biotherapies for Cancer--
"The beauty of this approach is that replication is constrained in CIK cells and rapid in tumor targets."
Chris Contag, Stanford University
Treating cancer may soon be a matter of finding the best horse and the best jockey for the job. Researchers have saddled a cancer-killing virus on the back of a tumor-targeting immune cell in one of the most powerful attempts yet to win the race against cancer. Their result illustrates the potential for improved cancer treatment through targeted biological therapies.
Most current cancer treatments, like chemotherapy, are unable to distinguish healthy cells from cancerous ones. They end up killing hair cells or cells that line the gut. Other therapies, like immune cell-based cancer treatments that are primed against certain tumor molecues, don't often generate a sufficiently strong anti-tumor response because they are not effective against a variety of tumor cells. A new wave of cancer treatments, however, could skirt these issues. These treatments, known targeted biological therapies, build on known methods of combining cancer-killing viruses with immune cells, which move unhindered through the body, delivering their viral cargo to tumors while leaving nearby healthy cells alone. However, even though these targeted therapies hold much promise, their use has been limited. Injection of engineered viruses into the bloodstream can be inefficient because these viruses may leave their immune host too soon and be eliminated by an immune response or infect noncancerous cells, so that only a small fraction of them is delivered to any given tumor.
Now virologists at Stanford University led by Steve Thorne have found a way to deliver sufficient amounts of cancer-killing virus straight to tumor cells. At present, the immune cytokine-induced killer (CIK) cells and the vaccinia virus are the "best in class." CIKs cells, unlike other types of immune cells, target a variety of tumors. They are also capable of carrying their viral cargo deep into tumor tissue, where it can't harm surrounding healthy cells.
Meanwhile, the vaccinia virus, which has had a long history as a vaccine for smallpox, is perfectly suited for cell destruction, and the Stanford team’s move to place it in CIKs has restricted its replication to tumors. That’s because, like other viruses, vaccinia can replicate in an immune cell host, but as Thorne found when he infected CIK cells with the virus, its replication in this immune cell is delayed. The vaccinia virus completes its life cycle in stages in the CIK host, saving a rapid burst of replication until 48 or 72 hours after infection, compared to 4-8 hours in other cell types. Since it remains hidden in the CIK cell until interaction with the tumor cells, it is more potent.
Targeting is also more efficient with this super duo; as reported in the March 24th issue of Science, 48 hours after Thorne injected the virus-infected CIK cells into mice, he detected very little virus in any other organ besides the tumor, and the virus was replicating deep inside it. When the virus was delivered alone, on the other hand, it did not burrow far enough into the tumor to be effective. To prove that neither individual CIK nor vaccinia would have been as effective as the combined effort, Thorne injected each as single therapies. While only 1 out of 8 total mice survived longer when treated with just CIK or just the virus, survival was significantly increased for 6 out of 8 mice with the combined therapy.
"This is an excellent example of how combination cancer therapies can have additive effects," says Inder Verma, a geneticist at The Salk Institute in La Jolla, Calfornia. "I think this is the way of future cancer treatments."
.MGW.
"The beauty of this approach is that replication is constrained in CIK cells and rapid in tumor targets."
Chris Contag, Stanford University
Treating cancer may soon be a matter of finding the best horse and the best jockey for the job. Researchers have saddled a cancer-killing virus on the back of a tumor-targeting immune cell in one of the most powerful attempts yet to win the race against cancer. Their result illustrates the potential for improved cancer treatment through targeted biological therapies.
Most current cancer treatments, like chemotherapy, are unable to distinguish healthy cells from cancerous ones. They end up killing hair cells or cells that line the gut. Other therapies, like immune cell-based cancer treatments that are primed against certain tumor molecues, don't often generate a sufficiently strong anti-tumor response because they are not effective against a variety of tumor cells. A new wave of cancer treatments, however, could skirt these issues. These treatments, known targeted biological therapies, build on known methods of combining cancer-killing viruses with immune cells, which move unhindered through the body, delivering their viral cargo to tumors while leaving nearby healthy cells alone. However, even though these targeted therapies hold much promise, their use has been limited. Injection of engineered viruses into the bloodstream can be inefficient because these viruses may leave their immune host too soon and be eliminated by an immune response or infect noncancerous cells, so that only a small fraction of them is delivered to any given tumor.
Now virologists at Stanford University led by Steve Thorne have found a way to deliver sufficient amounts of cancer-killing virus straight to tumor cells. At present, the immune cytokine-induced killer (CIK) cells and the vaccinia virus are the "best in class." CIKs cells, unlike other types of immune cells, target a variety of tumors. They are also capable of carrying their viral cargo deep into tumor tissue, where it can't harm surrounding healthy cells.
Meanwhile, the vaccinia virus, which has had a long history as a vaccine for smallpox, is perfectly suited for cell destruction, and the Stanford team’s move to place it in CIKs has restricted its replication to tumors. That’s because, like other viruses, vaccinia can replicate in an immune cell host, but as Thorne found when he infected CIK cells with the virus, its replication in this immune cell is delayed. The vaccinia virus completes its life cycle in stages in the CIK host, saving a rapid burst of replication until 48 or 72 hours after infection, compared to 4-8 hours in other cell types. Since it remains hidden in the CIK cell until interaction with the tumor cells, it is more potent.
Targeting is also more efficient with this super duo; as reported in the March 24th issue of Science, 48 hours after Thorne injected the virus-infected CIK cells into mice, he detected very little virus in any other organ besides the tumor, and the virus was replicating deep inside it. When the virus was delivered alone, on the other hand, it did not burrow far enough into the tumor to be effective. To prove that neither individual CIK nor vaccinia would have been as effective as the combined effort, Thorne injected each as single therapies. While only 1 out of 8 total mice survived longer when treated with just CIK or just the virus, survival was significantly increased for 6 out of 8 mice with the combined therapy.
"This is an excellent example of how combination cancer therapies can have additive effects," says Inder Verma, a geneticist at The Salk Institute in La Jolla, Calfornia. "I think this is the way of future cancer treatments."
.MGW.
posted by Meagan G at
10:14 AM
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