Author: Abinaya Helbig Edited by: Ruchi Maniar
Cancer possesses a deadly capability of hiding away and escaping from our body’s immune system, allowing it to both grow and spread uninterruptedly. For many years, scientists and researchers have been working towards a common goal of finding a therapeutic solution which would “educate” our immune system to detect cancer cells as foreign cells and elicit an immune response to attack those cancerous cells. (1) In fact, cancer cells can be detected by the immune system because of their surface expression of altered proteins termed neoantigens, which are generated from mutated DNA sequences. To the immune system, these neoantigens appear as foreign particles. As a result, neoantigens taken up by immune cells such as dendritic cells (DCs) could potentially elicit a strong T- cell response to attack those cancer cells that express them, but this can only be possible given there is further therapeutic assistance; this is because neoantigens have inherently low immunogenicity, i.e. causing a weak immune response.(2)
In recently published studies, researchers described the potential use of neoantigens as vaccine targets. This is a potenial way of protecting patients from their own cancers and decreasing the risk of cancer recurrence. (3)
A new vaccine has been developed which consists of programmable biomaterial made from very small mesoporous silica rods (MSRs). (4,5) These can be filled with tumour-expressed peptides (neoantigens) and then injected under the skin, upon which the MSRs assemble into a 3D scaffold to attract DCs. The MSRs are coated with polyethyleneimine (PEI), a material that allows an enhanced absorption of multiple peptides and DC activation T-cell response compared to the previous MRS vaccine lacking PEI. (6) The idea of using scaffolds to recruit immune cells has previously been explored by the Wyss Institute. (7) They also developed a 3D implantable, biodegrabable sponge-like scafflold for recruiting immune cells on site. This earlier vaccine entered Phase I clinical trials in 2013 and as of 2018, Novartis has signed an agreement to further translate this technology for clinical applcations. (8) However, as it is an already preformed scaffold, a minor surgery is required, unlike the case for the new MRS injectable, spontaneously assembling scaffolds.
The MSR-PEI vaccine, presented with a model peptide of E7 oncoprotein (known to cause cervical and other cancers) from human papillomavirus (HPV), completely eradicated large tumours and tumour metastases in about 80% of mice. The mice that were treated with the vaccine lived 150 days longer, while the untreated mice were killed earlier by the cancer. It was also observed that six months after the injection with MSR-PEI vaccine, the mice were still able to destroy tumour cells; this suggests that the mice developed an immunological memory of the respective tumour. The vaccine was also found to exhibit a synergistic effect with the additional use of immunotherapy (checkpoint therapy). Surprisingly, all of these effects were observed with just a single injection of the vaccine. (6)
(Image courtesy of the Wyss Institute for Biologically Inspired Engineering)
“This scanning electron micrograph image shows the MSR-PEI scaffold presenting tumor-expressed peptides. After injection under the skin of mice the biomaterial is filling with dendritic cells that can be seen here as small round shapes interacting with the spikey scaffold structure.” (1)
The vaccine was also tested on more aggressive mouse tumour models, which were deemed more representative of a human patient model. Five neoantigens that were identified in mouse melanoma and colorectal tumours were introduced into the biomaterial scaffold, which was then injected into the tumours. A single injection cleared tumour metastases and provided strong immune response against the tumours, with no major side-effects observed. (1,6)
With these promising results, Wyss Institute Core Faculty member David Mooney, Ph. D. and lead of the study, noted that using neoantigens in immunotherapy and being able to manipulate and modify predicted neoantigens in the scaffold, which acts as a delivery/ transport system, could soon enable higly effective personalized cancer treatments in humans.(1)
1. "Personal Cancer Vaccines Get Their Own Boost | Harvard John A. Paulson School Of Engineering And Applied Sciences". Seas.Harvard.Edu, 2018, https://www.seas.harvard.edu/news/2018/03/personal-cancer-vaccines-get-their-own-boost
2. "Personalized Tumor Vaccines Keep Cancer In Check". Science | AAAS, 2018, http://www.sciencemag.org/news/2017/04/personalized-tumor-vaccines-keep-cancer-check.
3. “ Personalized cancer vaccines show glimmers of success “ . Nature 2017, https://www.nature.com/news/personalized-cancer-vaccines-show-glimmers-of-success-1.22249#/b1
4. Kim et al., Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy, Nature Biotechnoloy, 33,64-72, 2015 https://www.nature.com/articles/nbt.3071#abstract
5. “Injectable 3D vaccines could fight cancer and infectious” Wyss Institute,2014 diseaseshttps://wyss.harvard.edu/injectable-3d-vaccines-could-fight-cancer-and-infectious-diseases/
6. Li et al., A facile approach to enhance antigen response for personalized cancer vaccination, Nature Materials, 17, 528-524, 2018 https://www.nature.com/articles/s41563-018-0028-2
7. "Implantable Cancer Vaccine". Wyss Institute https://wyss.harvard.edu/technology/implantable-cancer-vaccine/.
8. “Harvard bioengineers’ biomaterial-based cancer immunotherapies to be developed by Novartis” Wyss Institute 2018 https://wyss.harvard.edu/harvard-bioengineers-biomaterial-based-cancer-immunotherapies-to-be-developed-by-novartis/