Nanoparticles and RNA Used to Engineer an Immune Response to Cancer
An approach using nanoparticles to deliver RNA to immune cells, so as to kick off an immune response targeted to a specific cancer, has been in the news of late. Immunotherapies of a wide variety of types will form the basis for the coming generation of cancer therapies, the replacements for the present staples of chemotherapy and radiotherapy, but there is far too much work taking place to comment on every single project. It is a matter of accident rather than merit as to which research results receive greater or lesser attention from the public and the media. With the immune system being as complicated as it is, there are a lot of different ways in which to manipulate its activities, and most are in principle capable of producing viable therapies. Competition in this marketplace is as much to find a reliably, cost-effective way to address many cancers with the same technology platform as it is to find treatments that work.
Researchers have published a description of the first example worldwide of a clinically relevant and systemic mRNA cancer immunotherapy. They outline a novel approach to target a nanoparticle mRNA vaccine (RNA-LPX) body-wide to dendritic cells in the spleen, lymph nodes and bone marrow, where a highly potent, dual-mechanism immune response mimicking a natural antiviral immune response is rapidly elicited. The dual mechanism involves both adaptive (T-cell-mediated) and innate (type-I interferon (IFN)-mediated) immune responses, with the IFN response being essential for full anti-tumor effects of the vaccines. "Our study introduces a novel class of extraordinarily potent cancer vaccines that enables efficient redirection of the immune system against a wide range of tumor antigens. This is a major step towards our aim to make truly personalized cancer immunotherapies available and applicable to all cancer types."
The researchers further provide mode of action and efficacy data for this novel vaccine class in several preclinical tumor models and reports early data from a phase I dose-escalation, safety and tolerability trial (NCT02410733) of an intravenous RNA-LPX vaccine in melanoma patients. Crucially, in these patients, very low initial doses, lower than those used in preclinical studies, very rapidly elicited such a strong CD4+ and CD8+ T cell response that ex vivo culture was not required for detection. To date this vaccine has been very well tolerated and no severe toxicities have been observed. The phase I melanoma study continues to recruit patients and researchers plan to execute additional RNA-LPX vaccine studies for different cancer types.