June 04, 2016

Body's immune system induced to attack tumors and it is largely free from side effects - could lead to universal cancer vaccine

Scientists have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumours as if they were a virus, experts have said.

Writing in Nature, an international team of researchers described how they had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease.

The patients' immune systems responded by producing "killer" T-cells designed to attack cancer.

The vaccine was also found to be effective in fighting “aggressively growing” tumors in mice, according to researchers, who were led by Professor Ugur Sahin from Johannes Gutenberg University in Germany.

“[Such] vaccines are fast and inexpensive to produce, and virtually any tumor antigen [a protein attacked by the immune system] can be encoded by RNA," they wrote

The paper said the three patients were given low doses of the vaccine and the aim of the trial was not to test how well the vaccine worked. While the patients' immune systems seemed to react, there was no evidence that their cancers went away as a result.

In one patient, a suspected tumor on a lymph node got smaller after they were given the vaccine. Another patient, whose tumours had been surgically removed, was cancer-free seven months after vaccination.

The third patient had eight tumours that had spread from the initial skin cancer into their lungs. These tumours remained “clinically stable” after they were given the vaccine, the paper said.

The vaccine, which used a number of different pieces of RNA, activated dendritic cells that select targets for the body's immune system to attack. This was followed by a strong response from the "killer" T-cells that normally deal with infections.

Cancer immunotherapy is currently causing significant excitement in the medical community.

Nature - Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy


Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses1. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated2. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA3, 4, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

SOURCES - Nature, Johannes Gutenberg University, Independent UK

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