Swamidass: Better Personalized Cancer Vaccines From Genomes

One of the more exciting and important developments in recent years is personalized cancer vaccines. We sequence the tumor of each patient. We synthesize the fragments of the proteins that are mutated, and administer them to patients in a shot. This stimulates the immune system to attack the cancer by teaching what is the cancer.

This was working for patients, in many cases. We, however, realized a problem. The process of inferring the mutated protein, lays mutations of the patient on a default sequence. The reference genome was being used as a the default sequence from which to compute mutated protein fragments, rather than the patients own genome. In a surprisingly high number of patients, they were getting the wrong vaccine. This paper fixes this problem.

https://www.nature.com/articles/s41588-018-0283-9

Happy to answer any questions here about this work.

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Excellent work. You are doing real science that will make a difference in people’s lives. On behalf of humans everywhere, thank you. And please continuing this important work.

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And it’s in Nature Genetics. Dr. Hundal must be very pleased!

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My initial thoughts before diving into the paper . . .

Is there risk of precipitating deleterious autoimmune reactions? Is efficacy increased by expressing the full open reading frame of the cancer-mutated protein in a human cell line (e.g. HEK cells) to ensure the same folding and tertiary structure of the cancer-mutated protein?

The shift towards using the immune system to treat cancer is certainly an exciting new strategy. The advances in DNA sequencing have opened the doors to new treatments, and it is great to see researchers taking advantage of this technology.

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