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The development of various forms of immune therapy has helped activate the immune system against tumors. The use of immune checkpoint inhibitors (ICIs) has changed the focus of cancer research from the tumor to the host. However, ICIs are resistant in many individuals with nonimmunogenic tumor microenvironments (TMEs). Only 20% of patients with the most common solid tumors, such as breast, lung, and head and neck tumors, react to ICIs. Targeting immunosuppressive systems can improve therapeutic benefits.
In normal tissues, inhibitory mechanisms serve a regulatory function in enforcing self-tolerance and protecting against excessive immune activation and autoimmunity. Thus techniques that produce an immunogenic TME while avoiding significant side effects are critical when developing cancer therapies.
Scientists have developed a unique nanoparticle that could be applied to treat solid tumors in a novel way. Cancers of the breast, head, and neck all have solid tumors. The study was published in the journal Science Translational Medicine.
Nano-particle-delivering molecule increases rates of survival
Immune therapy has revolutionized cancer management, although only about 20% of individuals respond to the medication. The poor microenvironment of solid tumors makes them resistant to standard treatment, including immunotherapy. ATP levels are higher in malignancies treated with an anti-cancer approach.
Scientists aimed to create a combined therapy method that accelerates cancer therapy-induced immunogenic cell death in the TME, including ATP release. Limited ATP breakdown into adenosine resulted in a long-lasting immune response. Conventional cancer therapy can develop an immunosuppressive TME enriched with adenosine. This leads to tumor resistance or recurrence, despite its capacity to harm tumor cells. A shift in the TME’s balance toward ATP is critical for launching and maintaining a response against tumors.
These ATP levels are promptly destroyed into adenosine by a set of enzymes expressed in the cancer cell. Adenosine in the cancer environment can lead to poor treatment response. As a result of poor physicochemical qualities, chemicals like ARL67156 cannot enter solid tumors. The nanoparticle structure allows for selective joining and release of the chemical in solid tumors.
The particle delivered ARL67156, an enzyme inhibitor that blocks the breakdown of ATP into adenosine. Several mouse cancer models were used to test the particle. Nanomedicine significantly slowed cancer growth, allowing patients to live longer. The researchers also looked at how the particle interacted with an antibody, which is a typical treatment. The treatment worked well with antibody medication.
Finally, the scientists tested the medicine in a three-dimensional in-vitro model of malignancies from colon and breast cancer patients. There was an enhancement of tumor apoptosis by the anti-cancer immune response.
The findings show that nanoparticle therapy can treat human tumors and that it could also improve the efficacy of existing treatments. Better therapeutic outcomes are always welcome news in the management of tumors.
The use of nanoparticles effectively delivered the molecules into the cancer location. These findings led to better prognosis and therapeutic outcomes in patients.
Chengqiong Mao et al. ,Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression.Sci. Transl. Med.14,eabh1261(2022). https://doi.org/10.1126/scitranslmed.abh1261