- Scientists from
Fred Hutchinson Cancer Research Center have developed nanoparticles that
modify T cells.
- The modified T
cells fight against cancer cells and are a potential method of cancer
- This method
involves modification of the T cells within the body of the patient.
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.
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
‘Cancer cells are the body’s own cells, so T cells do not recognize them as abnormal. Nanoparticles alter T cells to fight against cancer cells.’
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.
alternative to the current treatment methodologies for cancer is necessary,
considering the side effects associated with chemotherapy
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.
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
Within the Body
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.
the study, Dr. Stephen and his colleagues
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
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
difference in the system in the current method of immunotherapy involves
contain genes that are necessary for the development of the chimeric
- 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
- 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.
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.
mice that were initially treated with chemotherapy were then later infused with
T cells that were altered and which expressed the CARs.
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.
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.
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.
- 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:
- CAR T-Cell Therapy: Engineering Patients' Immune
Cells to Treat Their Cancers - (https://www.cancer.gov/about-cancer/treatment/research/car-t-cells)