Antibody could be used to target tumor-causing protein, study shows

March 11, 2014

Cincinnati Cancer Center (CCC) and University of Cincinnati (UC) Cancer Institute researchers have found in a phase-1 study that patients with advanced melanoma and kidney cancer who were treated with a certain antibody that targets a tumor-enhancing protein was safe, which could lead to more treatment options for patients.

The study is published in the March 11 edition of PLOS ONE, a peer-reviewed, open access online publication.

Principal Investigator John Morris, MD, clinical co-leader of the Molecular Therapeutics and Diagnosis Program for the CCC, co-leader of the UC Cancer Institute's Comprehensive Lung Cancer Program, professor in the division of hematology oncology at the UC College of Medicine and UC Health medical oncologist, says this study sheds light on a therapy that could be used alone or in combination to help with a number of cancers.

"Transforming growth factor-beta (TGFβ) is a protein that helps cells maintain their functions, from formation to transition to death," Morris says. "Early in the transition of cancers from premalignancy to malignancy, TGFβ can suppress cell growth; however, in advanced cancers, these effects are typically lost, and TGFβ will directly promote the growth and spread of tumors.

"TGFβ-caused cellular changes have been described in many different tumor models and appear to be important for causing cell migration and promoting spread of . Increased TGFβ has been reported in many different cancers including prostate, breast, lung, pancreatic, renal cell, or kidney, liver and more, and elevated plasma TGFβ levels correlate with advanced tumor stage, metastases and poor survival. Given this data, the protein is being examined for potential therapeutic targets."

He adds that in preclinical models, using antibodies or receptors that hinder TGFβ have shown .

"In animal models, effects of anti-TGFβ combined with various chemotherapies, radiation or other biologic-related treatments, including vaccines, have been reported to improve the treatment of both primary and metastatic disease," Morris says. "GC1008, or fresolimumab, is a human antibody that neutralizes the active forms of human TGFβ.

"GC1008 was investigated as a treatment for cancer and fibrotic diseases. We wanted to test the safety of this treatment in repeated doses for patients with malignant (skin cancer) and renal cell carcinoma ()."

In the study, which was conducted at the National Cancer Institute and a number of cancer centers in the U.S., patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at varying doses. Patients who were stabilized, with no progression of the cancer, were eligible to receive extended treatment consisting of four doses of GC1008 every two weeks for up to two additional rounds.

Pharmacokinetic and exploratory biomarker assessments were performed.

"Twenty-nine patients, 28 with malignant melanoma and one with , were enrolled and treated with 22 in the dose-escalation portion and seven in a safety cohort arm, with one consistent dose delivered," Morris says. "No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe."

He adds that four patients developed reversible squamous-cell carcinomas (a type of skin cancer), one patient experienced a partial positive response to treatment and six had stable disease with a progression-free survival of 24 weeks.

"GC1008 showed an acceptable safety profile when administered up to 15 mg/kg every two weeks," Morris says. "This preliminary evidence of antitumor activity indicates that additional studies are needed to help determine the efficacy and safety of GC1008 alone and in combination with other treatments, as well as define dose and response."

Explore further: Cancer vaccine could use immune system to fight tumors

Related Stories

Cancer vaccine could use immune system to fight tumors

February 27, 2014
Cincinnati Cancer Center (CCC) and UC Cancer Institute researchers have found that a vaccine, targeting tumors that produce a certain protein and receptor responsible for communication between cells and the body's immune ...

Clinical trial examines use of human immune system to fight aggressive lung cancer

December 19, 2013
Researchers at the Cincinnati Cancer Center (CCC) and the UC Cancer Institute are conducting a clinical trial examining a method to stimulate the human immune system to destroy or block the growth of lung cancer cells.

Researchers test safety of Nivolumab in kidney cancer

June 3, 2013
Researchers at Dartmouth-Hitchcock Norris Cotton Cancer Center will present a poster on a phase I clinical trial of Nivolumab, a PD-1 receptor blocking antibody, being used in combination with other drugs in patients with ...

Engineered antibody demonstrated safety, efficacy in wide range of advanced tumors

April 10, 2013
(Medical Xpress)—The engineered antibody MPDL3280A, which targets a protein called programmed death-ligand 1 (PD-L1), was safe and effective for several cancers, according to phase I study results presented at the AACR ...

Kidney cancer care improves with vaccine-based approach

February 19, 2014
The Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute has opened a novel Phase III, vaccine-based clinical trial aimed at providing kidney cancer patients long-term control of their disease.

Investigational drug may increase survival for some patients with advanced melanoma

March 4, 2014
An experimental drug aimed at restoring the immune system's ability to spot and attack cancer halted cancer progression or shrank tumors in patients with advanced melanoma, according to a multisite, early-phase clinical trial ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...


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.