The ability to target cancer in mice without the modification of any active targeting ligands remains a challenge for in vivo applications of mRNA technology. For mRNA vaccines, targeted delivery to the lymph node is expected to reduce side effects and increase the immune response. In a new study, researchers demonstrate an endogenously lymph node-targeting lipid nanoparticle (LNP) for developing an mRNA cancer vaccine.
In a paper, a liquid nanoparticle-mediated lymph nodetargeting delivery of an mRNA cancer vaccination induces a robust CD8+ T cell response.
Qiaobing Xu, PhD, professor of biomedical engineering at Tufts School of Engineering, describes what we're doing now as the development of the next generation of mRNA vaccines that can target specific organs and tissues.
To date, more than 20 mRNA cancer vaccines have been studied in clinical trials. However, much of the mRNA ends up in the liver. Although liver antigens may still induce an immune response, there is still a risk of liver inflammation and damage. A more effective and long-lasting vaccination would target the lymphatic system, where immune cells are concentrated.
Targeting is achieved by altering the chemical structure of the LNPs that are present in the lymph nodes after being administered subcutaneously to mice. The researchers believe the LNPs collect molecules from the blood stream on their surface, and those selected molecules bind to specific receptors in the target organ.
The cancer vaccination used in this study, similar to the mRNA COVID-19 vaccinations, also contains mRNA in LNPs. The team examined an endogenously lymph node-targeting LNP named 113-O12B, which demonstrated increased and specific expression in the lymph node compared to the LNP formulated with ALC-0315a synthetic lipid used in the COVID-19 vaccine Comirnaty.
In this study, the targeted delivery of the mRNA vaccine elicits robust CD8+ T cell responses, exhibiting excellent protective and therapeutic effects on the B16F10 melanoma. 113-O12B can efficiently deliver both a full-length protein and a short-peptide-based antigens-encoded mRNA, thus providing a universal platform for mRNA vaccinations.
When combined with another existing treatment that prevents cancer cells from suppressing an immune response, mice with metastatic melanoma who were treated with the lymph-targeted vaccine demonstrated significant tumor inhibition and a 40% rate of complete response. No tumorswith no recurrence in the long-term
When metastatic tumor cells were injected later, all mice who were completely recovered were prevented from developing any additional tumors, proving that the cancer vaccination resulted in excellent immune memory.
Jinjin Chen, PhD, is a postdoctoral research fellow at the Xus lab. This cancer vaccine provides a much more efficient immune response, and it is designed to carry both large and small antigens.