Breakthrough in Breast Cancer Research: HER2 Vaccine Shows Promise in Clinical Trials

 The Exciting Possibility of a Breast Cancer Vaccine

Cancer prevention is a major goal in health research, and one major milestone was the HPV vaccine, which targets a virus responsible for different types of cancer, mainly cervical cancer. Recently, there's been excitement in the news about a possible breast cancer vaccine. How does this vaccine work? How successful is it, and when might it become available? That’s the topic of this week's Healthcare trip.

In November of 2022, an article was published in the journal Jama Oncology that covered the clinical trial results for a breast cancer vaccine that has been many years in the making. This was a phase one non-randomized clinical trial with 66 advanced stage breast cancer patients. Patients had what is called HER2 or HER2 positive breast cancer, with HER2 being the human epidermal growth factor receptor 2 protein, which is quite a mouthful. In short, an overabundance of this protein helps cancer cells grow, and its presence at high levels is responsible for 20 to 25 percent of all breast cancers.

This knowledge has led to many targeted therapies for HER2 positive breast cancer patients, and it’s the basis for the clinical trial at hand. The trial looks at the ability of a plasmid-based vaccine designed to increase HER2-specific T-helper cells. Let's break that down a little: a plasmid is a small circular DNA molecule that can be found in some microscopic organisms like bacteria. This circular DNA is different than the genomic DNA you might be more used to hearing about.

A plasmid-based vaccine is one that introduces a plasmid containing a specific DNA sequence. In this case, that sequence codes for a specific part of the HER2 receptor protein. The idea is that this will lead to a strong immune response against the whole protein via the creation of immune cells called T-cells that will specifically recognize and then target the HER2 protein.

To summarize, this vaccine is designed to train the immune system to recognize and attack breast cancer cells that express the HER2 protein, a protein known to cause around a quarter of all breast cancers.

Alright, so these 66 women in the trial had advanced-stage metastatic breast cancer that had either gone into remission or was largely reduced. They were each assigned to one of three vaccine doses, received three times, along with an immune-stimulating drug. Afterward, they were followed up for several years. At the end of the trial, more patients survived than would be expected at baseline for individuals with similar stages of cancer and no vaccine. Keep in mind that this is a non-randomized, non-controlled trial that measured immune cell levels, not cancer growth, so it's hard to pin anything to the vaccine just yet.

Instead, as is the purpose of a phase one trial, the idea here was to assess both safety and the ability of different doses to elicit a satisfactory immune response. And there’s good news on both fronts. Because the HER2 protein isn’t specific to breast cancer cells, it was important to make sure that eliciting this immune response didn’t wreak havoc on the rest of the body, and it did not. Side effects were limited and manageable for all doses, with many being common to currently approved vaccines.

The data on immune responses suggested that the two higher doses were the best performers. Though immunity levels after vaccination were lower in some patients who received the highest vaccine dose, which seemed to be associated with persistent plasmid DNA at the injection site, making the middle dose the probable favorite.

This is all super exciting, but definitely keep in mind that we don’t know yet if the vaccine stops or shrinks cancer growth. This is something we can look at in phase two trials, and good news — those are now underway. If those are successful, there will still be phase three trials and FDA approvals, so we still have a way to go. But we're well on our way.

Adrian enjoyed this episode, and you might enjoy this previous series on the history, present, and future of vaccines.