The cancer must develop neoantigens that are sufficiently distinct from human surface proteins and consistent across the cancer.
This is not necessarily true. There are some proteins that get produced by embryos and not by adult humans. Sometimes cancer mutates in a way that those proteins get produced by cancer cells.
While the vaccines that target a single of those embryo proteins did not do enough in clinical trials, I don’t see a reason why we should completely ignore those proteins.
Cancer cells must be isolated and have their surface proteins characterized.
Given that cancer cells engage in necrososis much more than regular cells you don’t need to isolate cancer cells to get the DNA of cancer. ctDNA can in theory be used to sequence the cancer. Using ctDNA might even be better because it gives you a better idea of whether a mutation is present in most of the cancer cells or only the section from which you removed cells.
Individualized cancer vaccines are not yet practical
Moderna has just put an individualized cancer vaccine into a phase III trial after positive results from a phase 2b trial:
Hirawat was referring to Moderna and Merck’s December announcement of positive results from a 157-patient phase 2b trial dubbed KEYNOTE-942. The pair said a combination of their personalized mRNA cancer vaccine, coded mRNA-4157 or V940, and the PD-1 inhibitor Keytruda slashed the risk of tumor recurrence or death by 44% compared with Keytruda alone when used as an adjuvant therapy in stage 3⁄4 melanoma following complete surgical resection.
ctDNA can in theory be used to sequence the cancer.
I don’t think that’s a good idea. It’s not the same and would be hard to separate from other cfDNA.
Moderna has just put an individualized cancer vaccine into a phase III
Do you think that trial is a bad idea?
What Moderna is doing is sequencing cancer cells and healthy cells, and using some algorithm to guess what mRNA vaccine would work. I think they’re not quite there yet: the hazard ratio with a checkpoint inhibitor isn’t much better than the checkpoint inhibitor alone, and I always discount the reported performance in small trials a bit. (And looking at the stock price, Wall Street seems to agree.) Note also that it’s specifically for certain types of melanoma, and comes after several failed cancer mRNA vaccine trials. That limitation to melanoma types indicates to me that their algorithm and its personalization are probably rather limited.
It’s not that I’m opposed to Moderna doing their trial per se, but I am a bit concerned that their patents could ultimately result in a net reduction in progress.
Following up on the current market state discussion related to Moderna, any thoughts on the Amgen treatment that FDA just approved today? Seems to be a much more targeted treatment but the general approach of targeting specific mutations seems to suggest a “family of drugs” that targets a number of different mutations. If that can cover mutations the cause 90% of cancers seems like it would be a huge win. (But I’m not sure if things work that way!)
That new Amgen drug targets a human protein that’s mostly only used during embryonic development. I think it’s expressed by most cancer cells in maybe around 0.2% of cancer cases. In many of those cases, some of the cancer cells will stop producing it.
Most potential targets have worse side effects and/or are less common.
This is not necessarily true. There are some proteins that get produced by embryos and not by adult humans. Sometimes cancer mutates in a way that those proteins get produced by cancer cells.
While the vaccines that target a single of those embryo proteins did not do enough in clinical trials, I don’t see a reason why we should completely ignore those proteins.
Given that cancer cells engage in necrososis much more than regular cells you don’t need to isolate cancer cells to get the DNA of cancer. ctDNA can in theory be used to sequence the cancer. Using ctDNA might even be better because it gives you a better idea of whether a mutation is present in most of the cancer cells or only the section from which you removed cells.
Moderna has just put an individualized cancer vaccine into a phase III trial after positive results from a phase 2b trial:
Do you think that trial is a bad idea?
I don’t think that’s a good idea. It’s not the same and would be hard to separate from other cfDNA.
What Moderna is doing is sequencing cancer cells and healthy cells, and using some algorithm to guess what mRNA vaccine would work. I think they’re not quite there yet: the hazard ratio with a checkpoint inhibitor isn’t much better than the checkpoint inhibitor alone, and I always discount the reported performance in small trials a bit. (And looking at the stock price, Wall Street seems to agree.) Note also that it’s specifically for certain types of melanoma, and comes after several failed cancer mRNA vaccine trials. That limitation to melanoma types indicates to me that their algorithm and its personalization are probably rather limited.
It’s not that I’m opposed to Moderna doing their trial per se, but I am a bit concerned that their patents could ultimately result in a net reduction in progress.
Following up on the current market state discussion related to Moderna, any thoughts on the Amgen treatment that FDA just approved today? Seems to be a much more targeted treatment but the general approach of targeting specific mutations seems to suggest a “family of drugs” that targets a number of different mutations. If that can cover mutations the cause 90% of cancers seems like it would be a huge win. (But I’m not sure if things work that way!)
That new Amgen drug targets a human protein that’s mostly only used during embryonic development. I think it’s expressed by most cancer cells in maybe around 0.2% of cancer cases. In many of those cases, some of the cancer cells will stop producing it.
Most potential targets have worse side effects and/or are less common.