Nanoparticles Hold The Key to Boost Immune Cells Against Cancer

A research team from Fred Hutchinson Cancer Research Center has designed nanoparticles that are biodegradable and which can be used to modify immune cells, to both identify as well as to destroy cells that are cancerous, when these cells are still within the body. The study showed that nanoparticle-programmed T cells could clear or delay the progression of leukemia, the findings of which were published in the journal Nature Nanotechnology.

Dr. Matthias Stephan, the senior author of the study said that this was the first study to utilize nanoparticle technology to provide T cells with tumor recognition capabilities, without the need for laboratory manipulations. The genetically modified cells function within 24 to 48 hours, with the receptors produced for weeks. The fast acting ability of these cells show that they can be used to mount a strong immune response that will effectively prevent the development of cancer cells, before they become fatal.

An alternative to the current treatment methodologies for cancer is necessary, considering the side effects associated with chemotherapy and radiotherapy procedures. Immunotherapy for cancer treatment has been found to show promise in clinical trials that have been conducted but they have been found to have the following limitations:

• It takes many weeks to design immunotherapy interventions
• The T cells, using the currently available procedures, are removed from the patient and then altered, before they are added back into the patient.
• This takes an extended period of time and is both time-consuming and expensive.

The current study involves the use of nanoparticles that are less expensive and do not take as much time as the traditional immunotherapies. This method of treatment is aimed at the start of cancer diagnosis, before it progresses to an advanced stage.

Genetic Engineering Within the Body

The nanoparticle engineered T cells would help in providing cellular immunotherapy for cancer patients. The genetic alterations in T cells that occur in a laboratory during traditional immunotherapeutic strategies are now carried out within the body, resulting in an army of T cells against cancer.

In the study, Dr. Stephen and his colleagues

• Developed nanoparticles that were bio-degradable
• Altered T cells into CAR (Chimeric Antigen Receptors) T cells
• Designed a promising cellular immunotherapy that has been previously shown to be effective against leukemia

Chimeric Antigen Receptors

The genetically altered T cells are modified to present receptors on their surface which are called chimeric antigen receptors (CARs). These protein receptors are utilized by the T cells to recognize tumor cells. In the traditional method of immunotherapy, these CAR T cells are cultured in the laboratory till they are present in billions. When there are significant CAR T cells, these cells are introduced into the patients. The T cells would then multiply within the body and, with the help of their chimeric receptor, recognize and kill the cancer cells.

The difference in the system in the current method of immunotherapy involves

• Nanoparticles contain genes that are necessary for the development of the chimeric antigen receptors.
• The nanoparticles are tagged which helps them in getting attached to T cells.
• The nanoparticles are then engulfed by the T cells
• Once inside the T cells, the nanoparticles are directed towards the nucleus, where they dissolve.
• The new Chimeric Antigen Receptor (CAR) genes from the nanoparticles integrate with the chromosomes that are present in the nucleus.
• The CAR genes provide the necessary information for the T cells to present cancer receptors on its surface, within a period of a day or two.

The team determined if the CAR carrying nanoparticles had been successfully reprogrammed, and then tested their efficacy. The study was conducted on mouse models affected with leukemia and the difference in the treatment among mice undergoing the different treatment strategies was studied.

• One group of mice was treated with traditional chemotherapy procedures.
• One group of mice was treated with the nanoparticles.

The mice that were initially treated with chemotherapy were then later infused with T cells that were altered and which expressed the CARs.

The findings of the study revealed that

• The mice which were treated with the nanoparticles modified T cells showed an improvement in survival by 58 days.
• This is a significant increase in survival from the 2 weeks that the control mice survived with leukemia.

Further studies need to be carried out before this method of treatment reaches the stage of human trials. The scientists are working to improve this method of therapy to help treat solid tumors. These nanoparticles can also be used, in the future, as a method to improve the immune system, as traditional vaccines take several months to do that.

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Infectious diseases like hepatitis or HIV could also be treated with these immune boosting nanoparticles, as all it needs is a small number of altered T cells.  This method of treatment can revolutionize treatment for infectious diseases and cancer, boosting the immune system to fight these harmful conditions.

References:

1. Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. McKnight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai, Matthias T. Stephan. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nature Nanotechnology, 2017; DOI: 10.1038/nnano.(2017).5
2. CAR T-Cell Therapy: Engineering Patients’ Immune Cells to Treat Their Cancers - (https://www.cancer.gov/about-cancer/treatment/research/car-t-cells)

Source-Medindia