Personalized ovarian cancer vaccines set for human trials

It vaccine to treat patients with ovarian cancer, according to a new study. Researchers from the University of Connecticut say the vaccine stems from a new technique that identifies protein mutations in cancer cells, and the method is already set to enter human trials.

The research team, including co-principal investigator Dr. Pramod Srivastava of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut (UConn), publish their findings in the Journal of Experimental Medicine.

In order to describe how the vaccine works, the researchers first explain the interaction between the immune system and cancer cells.

The immune system has to recognize cancer cells before it can attack them. The researchers note that there are a sequence of proteins – called epitopes – on the outside of each cell in the body, which the immune system reads to determine whether cells are good or bad.

Cancerous cells also have epitopes, but they are very similar to the epitopes found on healthy cells. This means the immune system can have trouble determining whether the epitopes on cancerous cells need to be destroyed.

However, the team says that cancer cell epitopes do have tiny errors, or mutations, which differentiate them from healthy cells. The problem is that the immune system does not know what these errors look like. They explain that the cancer cell epitopes could possess more than 1,000 subtle differences, but only 10 of them may be of significance to the immune system.

In their study, the researchers set out identify these significant differences with the aim of enabling the immune system to recognize them. “We want to break the immune system’s ignorance,” says Dr. Srivastava.

Vaccine made up of cancer cell epitopes induced cancer resistance in mice

Co-principal investigator and bioinformatics engineer Ion Mandoiu, associate professor of computer science and engineering at UConn, analyzed DNA sequences from the skin tumors of mice and compared them with the DNA sequences from the healthy tissue of the mice.

The team notes that this process has been conducted in previous studies, but researchers have only looked at the strength of the immune system in binding to epitopes of cancer cells. This only works in developing vaccines against viruses.

To create a vaccine against cancers, the team adopted a novel technique; they assessed the differences between the mice’s cancer cell epitopes and the epitopes of their healthy cells.

The researchers then developed a vaccine using the differing cancer cell epitopes found in the mice. When given this vaccine, they found the mice were strongly resistant to skin cancer.

“This has the potential to dramatically change how we treat cancer,” says Dr. Srivastava.

Testing the vaccine against ovarian cancer in humans

The team plans to test the vaccine in patients with ovarian cancer this fall, once it has been approved by the Food and Drug Administration (FDA).

Ovarian cancer is the fifth leading cause of cancer deaths among women in the US. A woman’s lifetime risk of ovarian cancer is around 1 in 72, according to the American Cancer Society.

Led by Dr. Angela Kueck, a gynecological oncologist at UConn, the study will involve analyzing the DNA of tumors from 15-20 women with ovarian cancer. The data will then be used to create a vaccine specific to each woman.

The researchers explain that they decided to focus on testing the vaccine against ovarian cancer because short-term response to treatment for the disease is usually good, but the cancer often rebounds within 1-2 years. This means the team have time to develop and administer the vaccine for each woman, and will be able to determine the effectiveness of the vaccine within 2 years.

If these vaccines prove to be safe and effective, the researchers say they will move on to a phase 2 clinical trial to investigate whether they prolong the lives of patients with ovarian cancer.

The method used in this study could also be used to develop personalized vaccines for other cancers, the team notes, although they say further research in this area is warranted.

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