Gaurav Sharma ’22

Cancer immunotherapy has been extensively explored and requires information of the tumor’s antigen presentation in order for a method to be selected. An approach that is more effective and has a broader range had not been found that did not have the constraint of needing the information of the tumor’s antigen presentation. Researchers at Johns Hopkins School of Medicine and Johns Hopkins University sought to find a novel immunotherapy approach using nanoparticles. 

The biodegradable nanoparticles were composed of poly(beta-amino ester)s (PBAEs) which induce the release of 4-1BBL and IL-12. These two molecules activate cell-mediated immune response to target cancerous cells through an increase in antigen presentation. Hence, these nanoparticles bypass the separate step of gathering needed information on antigen presentation in order to elicit immune responses. The effectiveness of these nanoparticles were tested in vivo and in vitro using mice with melanoma since melanoma is difficult to treat with existing immunotherapy techniques. Slower tumor growth was seen and there was a significant amount of trials where the tumor was completely removed. Researchers saw that the long-term survivors developed a vitiligo-like pattern in the area that had melanoma which indicates a specified immune response towards melanoma. However, the discolored patch of fur spread to other parts of the body which shows that the nanoparticles are not confined to location. It suggests that the nanoparticles affect the whole anti melanoma system which caused discoloration to spread. The nanoparticles were then used on mice with colorectal carcinoma to test the efficacy on other types of cancer. All mice survive and removed the first tumor. When injected with a second carcinoma tumor injection, the second tumor did not develop to indicate long-term immunity. 

These findings represent another novel method that can be used to treat all types of cancer. It represents a better approach due to lower costs and no side-effects that are usually present in current injection techniques and in antigen presentation. This nanoparticle methodology also has more potential in preventing metastasis and long-term immunity. Researchers will be continuing to perfect the types of PBAEs used in the nanoparticles that may increase effectiveness as well as testing it in human patients. 

[1] S. Tzeng et al. In situ genetic engineering of tumors for long-lasting and systemic immunotherapy

. Proceedings of the National Academy of Sciences. 117, 4043-4052 (2020). doi: 10.1073/pnas.1916039117

[2] Image retrieved from: https://www.pnas.org/content/pnas/117/8/4043.full.pdf