PNAS: Nanoparticles stimulate the immune system and help it attack tumors

, June 10, 2020 /PRNewswire/ --BiovalleyBIOON /- Suppresses the immune system, so these types of treatments are not suitable for all patientsMIT engineers have now come up with a way to improve the effectiveness of a cancer immunotherapyThey showed that if mice were treated with existing checkpoint inhibitors and newnano-
particles to further stimulate the immune system, the treatment would be more effective than using checkpoint inhibitors aloneThe researchers say this approach could benefit a larger percentage of patients with cancer immunotherapy": "These treatments are very effective in a small number of patients, while in others they are not working at allIt's not entirely clear why this difference is there," said DrColin Buss, lead author of the new studyMIT team devised a way to package and transmit small segments of DNA, enhance the immune response to tumors, create synergies, and make checkpoint inhibitors more effectiveIn the study of mice, they found that double therapy can stop tumor growth and, in some cases, other parts of the bodythe growth of tumorphoto source: PNAS
Professor Anddorothy Wilson of Health Science and Technology, Electrical Engineering and Computer Science at the Massachusetts Institute of Technology, is the author of the study published in PNASremoving brakes the human immune system is regulated to identify and destroy abnormal cells, such as cancer cells However, many of the molecules secreted by tumors suppress the immune system in the environment around the tumor , ineffectiveing The attack of T-cells The idea behind checkpoint inhibitors is that they can eliminate the "brake" of the immune system and restore the ability of T-cells to attack tumor
Some of these inhibitors for checkpoint proteins such as CTLA-4, PD-1, and PD-L1 have been approved for the treatment of various cancers These drugs act by turning off checkpoint proteins that prevent T cells from being activated "They're doing very well in some patients, and they've provided some so-called treatments for about 15 to 20 percent of specific cancer patients," said Bhatia However, much more needs to be done to get more patients to use this approach "
some studies have found that combining checkpoint inhibitors with radiation therapy can make them more effective Another way the researchers tried was to combine them with immunostimulants One of these drugs is the dna or RNA-specific sequence of DNA or RNA identified by the immune system as a foreign object However, clinical trials of these immunostimulants have not been successful , one possible reason being that these drugs have not met their intended goals The MIT team is looking for a way to achieve more targeted delivery of these immunostimulation drugs, allowing them to accumulate in tumors sites to do this, they packaged oligonucleotides in tumor-penetrating peptides that they had previously developed to transmit RNA to suppress cancerous genes These peptides interact with proteins on the surface of cancer cells, helping them to target tumors These peptides also include positive charge parts, which penetrate the cell membrane once they reach tumor Bhatia and Buss decided to use oligonucleotides in this study containa a specific DNA sequence that usually appears in the of bacteria, but does not exist in human cells, so the human immune system can recognize it and respond These oligonucleotides specifically activate immune cell receptors called toll-like receptors, which detect micro
biological invasion "
The evolution of these receptors has enabled cells to recognize the presence of pathogens like bacteria ," Buss said "This tells the immune system that there is a danger here: to launch an immune response to kill it "
a synergetic effect
after producing nano-
particles, the researchers tested them in several different models of cancer mice They tested the combination of oligonucleotides
nano
particles, checkpoint inhibitors, and two treatments So far, these two treatments have produced the best results together "When we combined these particles with checkpoint inhibitor antibodies, we found a significant improvement in anti-cancer response simply compared to using particles alone or checkpoint inhibitors alone," Buss said When we treated these mice with nanoparticles and checkpoint inhibitors, we were able to stop their cancer from getting worse photo source: PNAS
researchers also want to know if they can stimulate the immune system to target tumors that have spread to the body To explore this possibility, they implanted two tumors in mice, on either side of the body They injected the mice with checkpoint inhibitors throughout the body, but only nanoparticles in one tumor They found that once the treatment combination activated T cells, they could also attack the second tumor "It's encouraging that we're seeing some signs that you can stimulate in one place and then get a systematic immune response," said Bhatia "
researchers now plan to conduct safety tests on these particles, hoping to further develop them to treat patients whose tumors themselves do not respond to checkpoint inhibitor drugs To that end, they are working with Errki Ruoslahti of the Sanford Burnham Prebis Institute for Medical Discovery, who initially discovered tumor-penetrating peptides A company founded by Ruoslahti has used other versions of tumor -penetrating peptides in human clinical trials to treat pancreatic cancer "This makes us optimistic about the potential to scale up, produce and improve them to help patients," said Bhatia " (biovalleybioon.com) reference: Engineers design nanoparticles that the the immune system, helping it to the Colin G Buss el al., "
Nanoparticlee delivery of immunolioligonucleotides to checkpoint therapeutics ," PNAS (2020)