Cancer vaccine strategy blocks death of tumour-specific cytotoxic T cells

New research could serve as the stepping-stone in constructing vaccines with a greater likelihood of finding and attacking tumours in the human body.

According to Dr Esteban Celis and Dr Hussein Sultan of the Georgia Cancer Center at Augusta University, the key in this vaccine strategy is increasing the amount of time a cytokine called interleukin 2 (IL2) stays in the body. IL2 is a molecule in the immune system responsible for regulating the activity of some white blood cells known as killer T cells.

“After administering peptide-based vaccines in mouse models of cancer, we saw that sustained IL2 signalling dramatically increased the number of tumour-specific cancer-killing T cells (CD8+),” said Dr Sultan, a postdoctoral fellow in the laboratory of Dr Celis.

During their experiments, Dr Celis and Dr Sultan noticed there was also an increase in the T cells’ ability to resist cancer immune evasion caused by a protein called programmed death-ligand 1 (PD-L1). It is well known that the PD-L1 protein can be produced by tumour cells, allowing them to evade destruction by the killer T cells.

“Together, these results substantially improved the antitumor efficacy of peptide-based vaccines in tumour-bearing mice,” Dr Sultan said.

Dr Celis added, “In order to be effective, IL2 needed to be administered either as a complex of IL2 and anti-IL2 antibody or in the form of polyethylene glycol-modified IL2 (PEG-IL-2). These formulations prolonged the half-life of IL2, allowing sustained activation of the IL2 receptor on vaccine-generated T cells, allowing them to survive longer in the body and attack the tumour.”

According to Dr Celis, it is difficult for vaccines to induce antibodies against tumours because most of the tumour antigens are not foreign proteins, as is the case with viruses. On the other hand, T cells have the capacity to recognize other types of antigens.

“As we know, cancer cells are created when normal cells undergo certain mutations,” Dr Celis said. “So, they don’t always look foreign to our immune system.”

Both Dr Celis and Dr Sultan hope their observations in mouse models of cancer can find their way into clinical studies with human cancer patients.

“Working on this research project was very rewarding and exciting,” Sultan said. “I want to help the scientific community discover insights on how to use the body’s immune system to fight this devastating disease.”

The study has been published in Cancer Immunology Research.