New cancer 'vaccine' shows future promise in treating and preventing metastatic cancers

Preclinical, laboratory studies suggest a novel immunotherapy could potentially work like a vaccine against metastatic cancers, according to scientists at Virginia Commonwealth University Massey Cancer Center. Results from a recent study show the therapy could treat metastatic cancers and be used in combination with current cancer therapies while helping to prevent the development of new metastatic tumors and train specialized immune system cells to guard against cancer relapse.

Recently published in the journal Cancer Research, the study detailed the effects of a molecule engineered by lead author Xiang-Yang Wang, Ph.D., on animal and cell models of melanoma, prostate and colon tumors. The molecule called Flagrp-170 consists of two distinct proteins, glucose-regulated protein 170 (Grp170), known as a "molecular chaperone," and a "danger signal" derived from flagellin, a protein commonly found in bacteria. The researchers used modified viruses, or adenoviruses, that can no longer replicate to transport Flagrp-170 directly to the tumor site to achieve localized vaccination. The novel therapy caused a profound immune response that significantly prolonged survival in animal models.

"Successfully promoting antitumor immunity will help eradicate tumor cells, control cancer progression and help prevent tumor relapse," says Wang, Harrison Scholar, member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center and associate professor of Human and Molecular Genetics at VCU School of Medicine. "This immunotherapy has the potential to be used alone or in combination with conventional cancer treatments to develop and establish immune protection against cancer and its metastases."

Grp170 is currently being explored for its potential as a "cancer vaccine" because it has been shown to help the immune system recognize cancer antigens. Antigens are molecules from foreign objects such as bacteria, viruses or cancer that, when detected, provoke an immune response aimed at attacking them. However, because cancer cells can alter the microenvironment surrounding a tumor, they are able to suppress immune responses and continue replicating without being attacked by the body's natural defenses.

The chimeric chaperone Flagrp-170, created by strategically fusing a fragment of flagellin to Grp170, not only enhances antigen presentation, it also stimulates additional immune signals essential for functional activation of specialized immune cells, including dendritic cells, CD8+ T lymphocytes and natural killer (NK) cells. Dendritic cells act as messengers between the innate and adaptive immune systems. Once activated in response to a stimulus such as Flagrp-170, dendritic cells migrate to lymph nodes where they interact with other immune cells such as T lymphocytes to shape the body's immune response. CD8+ T lymphocytes and NK cells are known to respond to tumor formation and kill cancer cells by triggering apoptosis, a form of cell suicide.

"Overcoming cancer's ability to suppress the body's natural immune responses and restore or develop immunity for tumor eradication is the goal of cancer immunotherapy," says Wang. "More experiments are needed, but we are hoping Flagrp-170 may one day be used in formulating more effective therapeutic cancer vaccines."

Moving forward, Wang and his team are working to better understand the molecular mechanisms responsible for Flagrp-170's therapeutic effects. Additional studies are underway to more efficiently target and deliver Flagrp-170 to tumor sites in order to provoke a more robust and durable immune response.

Wang collaborated on this research with Paul Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and program co-leader of Cancer Molecular Genetics at VCU Massey Cancer Center, chairman of VCU's Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine; Xiaofei Yu; Chunquing Guo, Ph.D.; Huanfa Yi; and Jie Qian, Ph.D., all from VCU's Department of Human and Molecular Genetics and the VCU Institute of Molecular Medicine; and John R. Subjeck from the Department of Cellular Stress Biology at Roswell Park Cancer Institute.

This research was supported by NIH grants CA129111 and CA154708; the American Cancer Society, the Department of Defense and, in part, by funding from VCU Massey Cancer Center's NIH-NCI Cancer Center Support Grant P30 CA016059.

Most Popular Now

Amgen announces Repatha® (evolocumab) significantl…

Amgen (NASDAQ:AMGN) has announced that the FOURIER trial evaluating whether Repatha® (evolocumab) reduces the risk of cardiovascular events in patients with clinically ev...

Read more

Vitamin D discovery could prove key to new treatme…

A team led by Motonari Uesugi, professor and deputy director of Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS), found that a vitamin D metabol...

Read more

Nuts can inhibit the growth of cancer cells

Roasted and salted, ground as a baking ingredient or fresh from the shell - for all those who enjoy eating nuts, there is good news from nutritionists at Friedrich Schill...

Read more

The drugs don't work, say back pain researchers

Commonly used non-steroidal anti-inflammatory drugs, such as ibuprofen, used to treat back pain provide little benefit, but cause side effects, according to new research ...

Read more

An alternative theory on how aspirin may thwart ca…

Studies abound that point to a role for plain old aspirin in keeping deadly cancers at bay. While aspirin is not yet part of mainstream treatment for any cancer, it is re...

Read more

Novo Nordisk enters collaboration with University …

University of Oxford and Novo Nordisk today announced a landmark research collaboration focused on type 2 diabetes. The partnership will enable scientists from Novo Nordi...

Read more

Relationship expert teams up with Pfizer to addres…

Nationally-recognized relationship expert and author, Logan Levkoff, Ph.D., has partnered with Pfizer Inc. (NYSE:PFE) to fill a void in information available to people li...

Read more

Pfizer reports fourth-quarter and full-year 2016 r…

Pfizer Inc. (NYSE: PFE) reported financial results for fourth-quarter and full-year 2016 and provided 2017 financial guidance. Pfizer manages its commercial operations th...

Read more

Anti-inflammatory diet could reduce risk of bone l…

Anti-inflammatory diets - which tend to be high in vegetables, fruits, fish and whole grains - could boost bone health and prevent fractures in some women, a new study su...

Read more

Sex, drugs, and rock and roll chemistry in the bra…

The same brain-chemical system that mediates feelings of pleasure from sex, recreational drugs, and food is also critical to experiencing musical pleasure, according to a...

Read more

Drug shows promise for treating alcoholism

UCLA researchers have found that an anti-inflammatory drug primarily used in Japan to treat asthma could help people overcome alcoholism. Their study is the first to eval...

Read more

Novartis delivered solid 2016 performance

Novartis announced today that the net sales were USD 48.5 billion (-2%, 0% cc) in the full year, as volume growth of 6 percentage points was offset by the negative impact...

Read more

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]