Sundays reading :)10 Mar 2019 10:29
Only the beginning
Despite the encouraging progress in this field, Levy advises caution: “We still have yet to see a clinically significant cancer vaccine result. I think we will, but it hasn’t happened yet.” Several randomized controlled trials are now in the works that should clarify whether any of these strategies can consistently produce a measurable benefit, and to what extent. In the meantime, many questions remain.
It is uncertain when vaccines should be administered. Kandalaft and others believe that the best tactic is to act shortly after initial treatment—kicking the cancer when it’s down. “We should be vaccinating patients who are in remission and who are at high risk of relapse,” she maintains. In contrast, advanced disease gives tumors more of a home court advantage, allowing them to ensconce themselves in a more highly immunosuppressive environment. However, some of these tumors may still prove susceptible, and both Neon and BioNTech are now pursuing trials in metastatic disease. “We’ve observed that we have some advanced patients responding fast, after three months, with tumor shrinkage,” says Sahin.
The immunosuppression associated with advanced disease will likely necessitate combination with other immunotherapeutic agents to achieve a durable effect, although it seems likely that such pairings will also prove important in early disease settings. Indeed, many vaccine trials now in the works entail such combinatorial regimens.
Levy notes that amid the zeal to jam together different immunotherapies, researchers should be careful not to overlook other promising classes of cancer drugs with more indirect immunological effects. For example, his team has found that combinatorial treatment with a kinase inhibitor called ibrutinib, which is known to modulate the activity of a variety of immune cells, can enhance the potency of his group’s vaccination strategy. “It was very promising in the preclinical model,” says Levy. “We’ll see how it works in patients.”
Finally, it remains uncertain whether therapeutic vaccines might help crack immunologically “cold” tumors that have proven intransigent against other forms of immunotherapy. There are some signs that this could be the case, including a recent trial of a personalized vaccine that seems to elicit an immune response in patients with glioblastoma—one of the hardest targets out there.12
“If vaccines can really turn ‘cold’ tumors into ‘hot’ tumors, we will open the field for patients who really have no options,” predicts Kandalaft. “I would love to see that happen.”
https://www.genengnews.com/news/taking-a-new-shot-at-tumor-vaccines/
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