Researchers at Harvard have described a new cancer vaccine approach that uses an injectable biomaterial scaffold to deliver a payload of tumor-specific peptides that stimulate the immune system to respond rapidly to cancer cells.

Abstract Existing strategies to enhance peptide immunogenicity for cancer vaccination generally require direct peptide alteration, which, beyond practical issues, may impact peptide presentation and result in vaccine variability. Here, we report a simple adsorption approach using polyethyleneimine (PEI) in a mesoporous silica microrod (MSR) vaccine to enhance antigen immunogenicity. The MSR–PEI vaccine significantly enhanced host dendritic cell activation and T-cell response over the existing MSR vaccine and bolus vaccine formulations. Impressively, a single injection of the MSR–PEI vaccine using an E7 peptide completely eradicated large, established TC-1 tumours in about 80% of mice and generated immunological memory. When immunized with a pool of B16F10 or CT26 neoantigens, the MSR–PEI vaccine eradicated established lung metastases, controlled tumour growth and synergized with anti-CTLA4 therapy. Our findings from three independent tumour models suggest that the MSR-PEI vaccine approach may serve as a facile and powerful multi-antigen platform to enable robust personalized cancer vaccination.

Boosting the immune response to cancer

Recently, interest has grown in using neoantigens in immunotherapy, as their use has become increasingly predictable. In the new study, researchers injected a special programmable biomaterial structure, built from mesoporous silica rods (MSRs), that forms a 3D scaffold that summons and stimulates dendritic cells[1].

Dendritic cells are the antigen-presenting cells of the immune system; their primary function is to process tumor-specific peptides and present them on the surface of T cells. The MSRs are coated with polyethyleneimine (PEI), a polymer that is used to deliver DNA and proteins to target cells and is known to stimulate the immune system. The vaccine also had other factors that help to recruit dendritic cells and boost the immune response.

The team compared this vaccine against control vaccines that lacked the PEI coating and found that the PEI coating made it significantly more efficient at stimulating dendritic cells. This meant that the PEI coating was better able to encourage dendritic cells to stimulate T cells, leading to the creation of killer T cells that can detect the tumor-specific peptides.







In order to highlight the potential for clinical translation, the researchers also designed a vaccine that presented the peptide of the E7 oncoprotein from human papillomavirus (HPV), which is known to cause cervical cancer. A single injection of the vaccine led to the total destruction of all HPV tumors in mice. The untreated mice died from cancer within 30 days, but 80% of the mice that received the vaccine lived 150 days or longer. A control vaccine that lacked the PEI coating and a traditionally made vaccine produced an effect only about half as potent.

Impressively, up to six months later after a single injection, the vaccinated mice were still able to destroy HPV tumor cells, as they had formed an immunological memory of the tumors and their peptides.

Tackling more aggressive cancers

To simulate more aggressive cancers, and to highlight the potential of the therapy for translation to humans, the researchers introduced up to five neoantigens associated with mouse melanoma and colorectal tumors into the biomaterial scaffold. They observed that a single injection of the vaccine was able to clear tumor metastases and generated a robust immune reaction against the tumors that is comparable to multiple injections from current vaccines.

They also combined their vaccine with immune checkpoint therapy, a technique that also stimulates T cells to seek and destroy cancer cells; this combination created a synergy in which the effects of both were enhanced. The researchers believe that combining these two therapies could be the basis for a robust anti-cancer treatment.







Conclusion

Immunotherapy is a rapidly advancing area of research, and there have already been human trials of neoantigen therapy for other forms of cancer with promising results. The combination of the new vaccine system with checkpoint therapy adds another string to our bow in the fight against cancer.

The war on cancer really does seem to be taking a decisive turn in our favor, and immunotherapy looks set to become the standard of care in the next decade. This is a good thing, and the replacement of destructive chemotherapy and current, inefficient treatments cannot come soon enough.

Literature

[1] Li, A., Mooney, D. et al. (2018) A facile approach to enhance antigen response for personalized cancer vaccination. Nature Materials. doi:10.1038/s41563-018-0028-2.





