Artificial molecules boost cancer therapy

Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. Immunotherapies are breakthrough treatments that stimulate the patient's immune cells to attack the tumor through the recognition of tumor antigens.

Dendritic cells are specialized immune cells whose role is to capture antigens from foreign bodies and present them to the immune system's killer T cells, which will then attack and destroy the invaders. For the vaccine, dendritic cells are taken out of the patient, "force-fed" with tumor antigens, and finally re-injected back into the patient. The idea is to facilitate the ability of the dendritic cells to prime killer T cells against the tumor, which is notoriously skilled in concealing itself from the patient's immune system.

Dendritic cell vaccines have achieved some clinical success but not without several limitations. For example, the tumor antigens used to "feed" the dendritic cells are generally not taken from the patient's tumor but from lab-grown cancer cells that are only partially similar to those of the patient. This can limit the power of the vaccine because its tumor antigens may differ from those of the patient's tumor, meaning that the killer T cells would not be properly activated to recognize and attack the tumor.

A group of researchers led by Michele De Palma at EPFL have now created artificial receptors called EVIR (extracellular vesicle-internalizing receptors), which enable the dendritic cells in the vaccine to selectively and efficiently capture antigens from the actual patient's tumor. This is achieved by inserting the EVIR into the dendritic cell, where it recognizes a protein on small vesicles called exosomes.

Exosomes are profusely released by the tumor and contain a variety of tumor antigens. They are also increasingly implicated in the promotion of metastasis and other processes that may facilitate the growth and spreading of cancer. By capturing exosomes coming from tumors, the EVIR helps the dendritic cells to precisely acquire tumor antigens from the cancer cells. The dendritic cells then present these antigens more efficiently to killer T cells, thus amplifying the patient's immune response against their tumor.

Imaging techniques also revealed that EVIRs promote the direct transfer of tumor antigens from the exosome surface to the outer membrane of the dendritic cell. This is a fascinating and unconventional route for antigen presentation to T cells,  which does not require complex and rate-limiting molecular interactions inside the dendritic cell.

The EVIR technology can intercept a natural phenomenon - the release of exosomes from tumors - to the patient's benefit, it exploits pro-tumoral exosomes as selective nanocarriers of tumor antigens, making them available to the immune system for cancer recognition and rejection. Although the new technology has the potential to increase the efficacy and specificity of dendritic cell vaccines, further pre-clinical work is required before it can be translated into a cancer treatment.
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Berry boosts cervical cancer therapy

According to the Centers for Disease Control and Prevention many women are diagnosed with cervical cancer each year. One of the most common treatments for cervical cancer is radiation. While radiation therapy destroys cancer cells, it also destroys nearby healthy cells. University of Missouri School of Medicine researchers studied in vitro human cancer cells to show that combining blueberry extract with radiation can increase the treatment's effectiveness.

Radiosensitizers are non-toxic chemicals that make cancer cells more responsive to radiation therapy. In a previous study, Fang and his research team showed that resveratrol, a compound in red grapes, could be used as a radiosensitizer for treating prostate cancer. Blueberries also contain resveratrol. In addition to resveratrol, blueberries also contain flavonoids.

The researchers used human cervical cancer cell lines to mimic clinical treatment. The cell lines were divided into four groups that included a control group, a group that received only radiation, a group that received only blueberry extract, and a group that received both radiation and the extract. Researchers used three different measures to confirm results of the study.

 Radiation decreased cancer cells by approximately 20 percent. Interestingly, the cell group that received only blueberry extract had a 25 percent decrease in cancer. However, the biggest decline in cancer cells occurred in the radiation and extract group.
The mechanism that makes blueberry extract a radiosensitizer also reduces the abnormal explosion of cell growth. Cancer cells avoid death by remodeling themselves. Along with reducing cell proliferation, the extract also 'tricks' cancer cells into dying. So it inhibits the birth and promotes the death of cancer cells.
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RNA molecules can kill cancer

Small RNA molecules developed as a tool to study gene function trigger a mechanism hidden in every cell that forces the cell to commit suicide.
The mechanism RNA suicide molecules can potentially be developed into a form of cancer therapy. Cancer cells treated with the RNA molecules never become resistant to them because they simultaneously eliminate multiple genes that cancer cells need for survival.

The inability of cancer cells to develop resistance to the molecules is a first, researchers discovered sequences in the human genome that when converted into small double-stranded RNA molecules trigger what they believe to be an ancient kill switch in cells to prevent cancer.

Testing a class of small RNAs, called small interfering (si)RNAs, researchers use to suppress gene activity. siRNAs are designed by taking short sequences of the gene to be targeted and converting them into double- stranded RNA. These siRNAs when introduced into cells suppress the expression of the gene they are derived from.

A large number of these small RNAs derived from certain genes did not, only suppress the gene they were designed against. They also killed all cancer cells. These special sequences are distributed throughout the human genome, embedded in multiple genes.
When converted to siRNAs, these sequences all act as highly trained super assassins.

They kill the cells by simultaneously eliminating the genes required for cell survival. By taking out these survivor genes, the assassin molecule activates multiple death cell pathways in parallel. The small RNA assassin molecules trigger a mechanism calls DISE, for Death Induced by Survival gene Elimination. Activating DISE in organisms with cancer might allow cancer cells to be eliminated.
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