Genetically engineered immune cell therapy found to boost survival in mice with brain tumors

February 24, 2016, Nagoya University
Chimeric antigen receptor (CAR) T cells CAR comprising a podoplanin (PDPN)-specific antibody fragment with CD28, 4-1BB, and CD3ζ intracellular domains are genetically engineered to target PDPN, a protein usually found in abundance in solid tumors, including GBM, which presents the worst prognosis among GBM subtypes. Infusion of CAR T cells into an immunodeficient mouse model led to inhibition of tumor growth. CAR T cell therapy that targets PDPN represents a promising immunotherapy for treating GBM.

Nagoya University-led research team shows in mice the potential of a special immune cell that targets a key protein in tumor growth that helps stop brain cancer.

For decades most cancers have been treated with a core standard of treatments that include surgery, radiation, and chemotherapy. Now, immunotherapy—a type of treatment that harnesses the patient's immune system to combat the disease—represents the future of cancer treatment, with its efficacy being demonstrated in even the most aggressive types of cancer.

Brain cancer comes in many forms, ranging from more easily treatable benign forms that may trigger gradual loss of brain functions, to malignant forms that can in many cases prove fatal. While there have been improvements in the current standard treatments, patients with glioblastoma (GBM), the most common and aggressive form of brain tumor, still suffer from a median survival rate of only 14.6 months and 5-year overall survival rates of less than 10%. There is therefore pressing need for novel therapies that improve the outcomes.

Researchers at Nagoya University have been studying the therapeutic effect of T cells, vital disease-fighting components in our body's immune system, for fighting cancer.

"Immunotherapy has emerged in recent years as a promising strategy for treatment of GBM," says Atsushi Natsume, corresponding author of the study and a member of the Nagoya University School of Medicine's Department of Neurosurgery. "We have successfully engineered T cells that produce special receptors on their surface, called chimeric antigen receptors (CARs), which allow the T cells to recognize specific proteins (antigens) expressed in GBM. We designed chimeric antigen receptor (CAR) T cells that specifically target podoplanin (PDPN), a for the progression of solid tumors, including GBM."

The research team found that injection of CAR T cells into 79 immunodeficient mice arrested the growth of GBM in 60% of them. Furthermore, the T can recognize PDPN on the tumor surface even with the absence of the body's own immune recognition system, which is usually compromised in cancer.

"Considering that PDPN is associated with poor prognosis in GBM, CAR T-cell therapy that targets this protein is promising for treatment of patients with relapsed or resistant tumors following first-line chemotherapy," says Toshihiko Wakabayashi, a coauthor and the chair of Department of Neurosurgery   Nagoya University School of Medicine. "There are certainly challenges to overcome for clinical application of this kind of immunotherapy, but the newly published data are an important milestone in immunotherapy targeting solid tumors that have eluded other treatments."

Explore further: Researchers find promise in new treatments for glioblastma multiforme

More information: S. Shiina et al. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains, Cancer Immunology Research (2016). DOI: 10.1158/2326-6066.CIR-15-0060

Related Stories

Researchers find promise in new treatments for glioblastma multiforme

October 1, 2014
Glioblastma multiforme (GBM) is one of the most lethal primary brain tumors, with median survival for these patients only slightly over one year. Researchers at Boston University School of Medicine (BUSM), in collaboration ...

Gene therapy: T cells target mutations to fight solid tumors

February 19, 2016
The efficacy of the immune system to combat disease makes the body's own healing powers a promising approach in the fight against cancer. A Berlin research group led by Wolfgang Uckert, Thomas Blankenstein and Matthias Leisegang ...

Study targets SGEF protein in treating glioblastoma brain tumors

January 13, 2016
The Translational Genomics Research Institute (TGen) has identified a protein called SGEF that promotes the survival of glioblastoma tumor cells and helps the cancer invade brain tissue.

Researchers create a promising new treatment for the deadliest form of brain cancer

September 2, 2015
UCLA scientists have developed a potentially promising new combination therapy for glioblastoma, the most common and deadliest form of brain cancer.

Glioblastoma: Study ties three genes to radiation resistance in recurrent tumors

February 3, 2015
A new study identifies three genes that together enable a lethal form of brain cancer to recur and progress after radiation therapy.

Metabolic compensation underlies drug resistance in glioblastoma

March 23, 2015
Gliobststoma (GBM) is a highly aggressive brain tumor that is resistant to many conventional cancer therapies. The kinase mTOR induces pathways that are aberrantly activated in GBM. However, mTOR inhibitors have not shown ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.