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 Annual Meeting 2013, held in Washington, D.C., April 6-10.

"Our PD-L1 antibody was well tolerated, and there were no limiting toxicities," said Michael S. Gordon, M.D., research director at Pinnacle Oncology Hematology in Scottsdale, Ariz. "It was active with antitumor activity across a broad range of cancers, and we have developed biomarker tools that we are testing, which may allow us to optimize patient selection for this ."

PD-L1, a protein found on the surface of many , impairs the immune system's ability to fight cancer, according to Gordon.

"PD-L1 is essentially a plug, which inserts into an outlet (PD-1) on the surface of the immune T cells," Gordon said. "As the come close to the tumor, for example, they are engaged by PD-L1, which inserts into the outlet on the surface of the T cell. That starts a signal inside the T cell that blocks the T cell's ability to kill the cancer cell."

MPDL3280A, a under development by , a member of the Roche Group, binds to PD-L1 and blocks this action.

Gordon and colleagues administered an escalating intravenous dose of MPDL3280A once every three weeks to 30 patients with a variety of locally advanced or metastatic solid tumors. They escalated the dose from 0.01 mg/kg to as high as 20 mg/kg. The data being presented are the preliminary data from the dose escalation cohorts of the ongoing phase I trial.

No dose-limiting toxicities or grade 4 have been reported. "We were able to escalate to the top dose without being limited by any serious side effects," Gordon said.

"From a therapeutic standpoint, we were able to identify a number of patients with a broad range of diseases, including lung cancer, , and stomach cancer, who responded to the treatment," he said.

A second protein, called PD-L2, fits into the same T-cell "outlet" as PD-L1, according to Gordon. MPDL3280A is specific for PD-L1; it does not block PD-L2, which is expressed in noncancerous tissues including the lung, he added.

"One would anticipate, compared with drugs being developed to specifically block the T-cell outlet (PD-1) and, therefore, block the relationship between the outlet and both PD-L1 and PD-L2, that we might see less lung or pulmonary toxicity with MPDL3280A. But we need to conduct larger studies to confirm this."

Explore further: Cancer therapy that boosts immune system ready for wider testing

Related Stories

Cancer therapy that boosts immune system ready for wider testing

June 2, 2012
Two clinical trials led by Johns Hopkins Kimmel Cancer Center researchers in collaboration with other medical centers, testing experimental drugs aimed at restoring the immune system's ability to spot and attack cancer, have ...

Researchers find success with new immune approach to fighting some cancers

June 13, 2012
A national research collaboration of senior researchers, including a researcher from Moffitt Cancer Center, has found that 20 to 25 percent of "heavily pre-treated" patients with a variety of cancers who enrolled in a clinical ...

New immune therapy shows promise in kidney cancer

June 4, 2012
An antibody that helps a person's own immune system battle cancer cells shows increasing promise in reducing tumors in patients with advanced kidney cancer, according to researchers at Beth Israel Deaconess Medical Center.

Scientists discover effects of PD-1 blockade on ART therapy in SIV-infected monkeys

March 8, 2012
Scientists have discovered that blocking PD-1 (programmed death-1), an immune molecule that inhibits the immune response to viral infections, can have a significant effect on HIV-like illness in nonhuman primates.

Innovative new strategy to treat Parkinson's disease

December 19, 2011
Stabilizing the cell's power-generating center protects against Parkinson's disease (PD) in a rat model, according to a report published online this week in the Journal of Experimental Medicine.

Recommended for you

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

Searching for the 'signature' causes of BRCAness in breast cancer

August 21, 2017
Breast cancer cells with defects in the DNA damage repair-genes BRCA1 and BRCA2 have a mutational signature (a pattern of base swaps—e.g., Ts for Gs, Cs for As—throughout a genome) known in cancer genomics as "Signature ...

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.