Combination therapy shows promise in fighting neuroblastoma

October 11, 2016, Children's Hospital Los Angeles

A study by a multidisciplinary team of researchers from The Saban Research Institute of Children's Hospital Los Angeles sheds further light on the role of the cytokine TGFβ1 in the growth of neuroblastoma, and suggests the possibility for a small molecule drug/antibody combinatorial therapy to treat this cancer. Their data has been published online by the journal Clinical Cancer Research.

Neuroblastoma (NB) is a type of solid cancer that arises from nerve tissues. It is the most common type of childhood cancer with nearly half of its incidence in children under two years of age and accounts for 15 percent of all deaths. Currently available therapy involves the use of an antibody called dinutuximab which targets a type of modified carbohydrate sugar (GD2) found to be expressed at high levels in NB tumors. However, this antibody-based treatment is often not sufficient to prevent cancer relapse.

In addition to directly targeting molecules involved in disease, in many cases antibody-based therapy is thought to also involve the activation of natural killer (NK) cells. NK cells are a subset of immune cells that have a proven capacity to kill tumor cells upon activation by antibodies. Proteins such as TGFβ1 (transforming growth factor beta 1) have recently been shown to suppress the anti-cancer functions of NK cells in the tumor microenvironment.

TGFβ1, part of the superfamily of cytokines, is a secreted protein that performs many cellular functions including control of cell growth, proliferation, and cell death. The CHLA researchers demonstrate a unique mechanism for tackling NB by employing a combinatorial therapy involving dinutuximab and a small molecule drug, galunisertib, which inhibits TGFβ1. Grafting NB cell lines or tissue from a patient with neuroblastoma into immunodeficient mice, the authors demonstrate that galunisertib-mediated inhibition of TGFβ1 allows dinutuximab and NK cells to effectively kill the NB tumors.

"The addition of galunisertib to adoptive cell therapy using in addition to the drug dinutuximab reduced tumor growth and increased the survival of mice injected with either neuroblastoma cell lines or patient-derived tumor tissue," said principal investigator Robert Seeger, MD, of CHLA's Center for Childhood Cancer and Blood Disease. Seeger is also a professor of pediatrics with the Keck School of Medicine of the University of Southern California (USC). He added that galunisertib reverses the TGFβ-1-induced suppression of cytotoxicity and may improve antibody-based immunotherapy for neuroblastoma.

Explore further: Basic research led to first FDA-approved immunotherapy for pediatric cancer

More information: R. C. Seeger et al, TGF R1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells, Clinical Cancer Research (2016). DOI: 10.1158/1078-0432.CCR-16-1743

Related Stories

Basic research led to first FDA-approved immunotherapy for pediatric cancer

January 27, 2016
Building upon more than two decades of basic research conducted at Children's Hospital Los Angeles, Araz Marachelian, MD, of CHLA, and her colleagues at pediatric academic centers across the U. S., have shown that an immunotherapy ...

A novel immunotherapy technique to treat patients with osteosarcoma and neuroblastoma

February 26, 2015
A novel phase 1 clinical trial that leverages T-cell immunotherapy is now under way at Karmanos Cancer Institute (KCI) in Detroit and Memorial Sloan-Kettering Cancer Center in New York City; bringing new hope to children ...

Scientists present new research on childhood neuroblastoma

July 13, 2016
In the journal Cell Reports researchers at Karolinska Institutet together with international colleagues present new data on the pediatric tumor neuroblastoma. Neuroblastoma is a nerve cell cancer that affects young children ...

New CAR T cell therapy using double target aimed at solid tumors

June 21, 2016
Chimeric antigen receptors (CARs), engineered from a patient's own immune cells, have been successful for treating blood cancers, but using CARs for solid tumors has been limited by side effects to normal tissues containing ...

Improving natural killer cancer therapy

May 16, 2016
Researchers at Vanderbilt University Medical Center have discovered a potential way to "tune up" the immune system's ability to kill cancer cells.

Antibody-drug compounds and immunotherapy to treat breast cancer

November 25, 2015
To more efficiently treat breast cancer, scientists have been researching molecules that selectively bind to cancer cells and deliver a substance that can kill the tumor cells, for several years. Researchers from the University ...

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

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.