The days of cancer relapse are over, thanks to this novel chemoimmunotherapy

Although chemotherapy is a popular and effective cancer treatment method, it has been found that cancer tumor cells tend to regrow after some time in many patients, even after the chemo. According to a team of researchers from the University of Pittsburgh School of Pharmacy (UPSP), this tumor relapse happens because of a protein called Xkr8.

The researchers have developed a novel chemoimmunotherapy approach that employs special “dual-action nanoparticles” to block the activity of Xkr8 in tumor cells, according to a press release. Song Li, the senior author and professor at UPSP, told IE, “Our nanoparticles can both kill tumor cells and activate the anti-tumor activity.” 

The scientists at UPSP were able to reduce the size of cancer tumors in mice using their new cancer treatment approach.  

The protein behind cancer relapse

Chemotherapy eliminates almost all tumors, but a special mechanism of the carcinogenic cells allows them to leave their residue and cause tumor relapse from the same. The current study reveals when a chemotherapy drug attacks a tumor, an immunosuppressant known as phosphatidylserine (PS) comes out of the tumor’s inner cell membrane layer. 

It starts accumulating on the cell surface and acts as a protective shield for the remaining part of the tumor. PS prevents the chemotherapy drug from completely wiping out the cancer cells. This is why the remains of some cancer cells are left behind, which later give rise to new tumors.

Professor Li and his team figured out that to prevent the recurrence of cancer, they need to stop PS from migrating to the cell surface. They dug deep and discovered that the accumulation of PS on the tumor cell surface is actually controlled by a protein called Xkr8. Interestingly, another study published earlier this month also highlighted that inhibition of the Xkr8 protein in mice leads to an “anti-tumor effect.” 

The dual-action chemoimmunotherapy 

The author of the current study noticed that the activity of Xkr8 increased every time a patient was given chemotherapy medicines fluorouracil and oxoplatin (FuOXP). After studying the limitations of the existing chemotherapy method and the Xkr8 protein behavior, they designed a new immunotherapy treatment and tested it on mice.

The researchers developed numerous nanoparticles by combining short-interference RNA (siRNA) and the FuOXP drug. The siRNA was entirely designed by them, and its goal was to cease the production of the Xkr8 protein. FuOXP, on the other side, was already available as a chemotherapy drug that promoted immune system action against tumors (basically, it was involved in killing the tumors).

The surface of the nanoparticles was loaded with chondroitin sulfate (CS) and polyethylene glycol (PEG) to ensure their safe and easy delivery to the target tumor cells. These chemicals allow the nanoparticles to ignore healthy cells and only bind with cell receptors on cancerous blood vessels and tissues. Moreover, CS and PEG also enabled a significant number of nanoparticles to reach the targeted tumor cells.

For instance, it has been noticed that out of 100, only 0.7 percent of nanoparticle medicines reach their target inside the body. Surprisingly, ten percent of the dual-action nanoparticles managed to successfully hit their target during the mice experiment. 

The researchers observed two groups of mice; the first group underwent chemoimmunotherapy (with nanoparticles), and the second group was treated with conventional chemotherapy that involved the use of only FuOXP. Movement of PS from the membrane to the tumor cell surface was found to be reduced to a large extent in mice belonging to the first group.

Some of the mice even had colon and pancreatic cancer. The chemoimmunotherapy treatment led to increased production of anti-cancer T cells in such mouse models. Moreover, the size of tumors was reduced in all the mice that received the dual-action therapy. 

“Our research may lead to the development of a new chemoimmunotherapy combination therapy that can be applied to the treatment of various types of cancers, including colon and pancreatic cancers,” Professor Li told IE. 

Taking the therapy to another level   

The dual-action chemoimmunotherapy is a combination of a new immunotherapy treatment and the existing chemotherapy approach. However, the researchers believe that it can also be further combined with other therapy methods like PD-1 immunotherapy.

PD-1 is an abbreviation for "programmed cell death protein 1," which is considered a checkpoint molecule. It serves as a brake and limits the magnitude of the immune response against the tumor cells. So when the PD-1 expression level is high, it limits the magnitude of the anti-tumor immune response.

When Professor Li and his team added a PD-1 inhibitor to the FuOXP-siRNA nanoparticle and tested this therapy on mice, they noticed positive changes in the condition of the animal models, and the chances of them surviving cancer also improved. These results hint at the future potential of the dual-action treatment.

However, the research work that highlighted this treatment is largely proof of concept, and more safety tests and toxicity studies need to be conducted before it can be moved to clinical trials.

The study is published in the journal Nature Nanotechnology.