Jump-starting cheaper cancer vaccines

September 26, 2012, Agency for Science, Technology and Research (A*STAR), Singapore
Dendritic cells (top left), derived from human embryonic stem cells, could provide an economical route to produce human cancer therapeutics. Credit: iStockphoto.com/drliwa (main image)

Dendritic cells (DCs)—workhorses of the immune system—derived from human embryonic stem cells (hESCs) may provide an economical way of generating off-the-shelf therapeutic vaccines against cancers, according to research led by Jieming Zeng and Shu Wang from the A*STAR Institute of Bioengineering and Nanotechnology, Singapore.

DCs process and present antigens—substances that stimulate immune responses—to other cells of the immune system that will then eliminate pathogenic cells carrying these antigens. This ability makes DCs ideal as vaccines within the body. As such, the US recently approved the first DC-based vaccine for use. DCs sourced from another individual, however, may be attacked by the immune system of a recipient. Consequently, DC-based vaccines have been prepared using cells derived from the recipient's own body. This is expensive, the supply of cells is limited, and highly variable results have complicated the evaluation of clinical trials.

Using hESCs, however, it is possible to produce a steady supply of DCs in unlimited numbers, under strict quality control. But, since these DCs are still susceptible to , Zeng, Wang and co-workers enlisted the aid of invariant natural killer T (iNKT) cells. These cells can be stimulated by compounds attached to molecules of the glycoprotein CD1d and used to boost the activity of DCs, thereby enabling them to trigger the immune response before being eliminated.

First the researchers added genes to DCs generated from hESCs to produce extra CD1d. The greater amount of this glycoprotein produced by the cells then triggered an expansion of iNKT cells in the presence of α-galactosylceramide (α-GC), a ligand or compound which binds to iNKT cells.

Subsequently, they found that α-GC was unnecessary for inducing an anti-. This is advantageous because previous studies by others with mice had shown that using α-GC for this purpose can lead to uncontrolled iNKT activation. In fact, the researchers showed that pulsing the modified DCs with melanoma antigen was sufficient to prime immune T cells against melanoma tumor cells. The same strategy worked with DCs derived from human monocytes, a type of white blood cell.

"The ability to generate large amounts of uniform hESC-DCs competent in inducing antitumor immunity indicates that they could be used as an unlimited cell source to produce off-the-shelf DC vaccines, to overcome the drawbacks of using an individual's own cells," Wang says. "We are now focusing on developing a simpler process to produce DCs with similar or even better capabilities."

Explore further: Scientists discover dendritic cells key to activating human immune responses

More information: Zeng, J., Shahbazi, M., Wu, C., Toh, H. C. & Wang, S. Enhancing immunostimulatory function of human embryonic stem cell-derived dendritic cells by CD1d overexpression. The Journal of Immunology 188, 4297–4304 (2012). www.jimmunol.org/content/188/9/4297

Related Stories

Scientists discover dendritic cells key to activating human immune responses

July 16, 2012
Scientists at A*STAR’s Singapore Immunology Network (SIgN), in collaboration with Newcastle University, UK, the Singapore Institute of Clinical Sciences and clinicians from multiple hospitals in Singapore, have identified ...

Rare immune cell is asset and liability in fighting infection

August 26, 2011
The same trait that makes a rare immune cell invaluable in fighting some infections also can be exploited by other diseases to cause harm, two new studies show.

Dendritic cell subtype protects against atherosclerosis

November 10, 2011
Atherosclerosis, commonly referred to as "hardening of the arteries," is a major risk factor for heart attack and stroke. The cause of atherosclerosis is not well understood but, for some time, chronic inflammatory immune ...

Recommended for you

Improving vaccines for the elderly by blocking inflammation

January 22, 2018
By identifying why skin immunity declines in old age, a UCL-led research team has found that an anti-inflammatory pill could help make vaccines more effective for elderly people.

Novel genomic tools provide new insight into human immune system

January 19, 2018
When the body is under attack from pathogens, the immune system marshals a diverse collection of immune cells to work together in a tightly orchestrated process and defend the host against the intruders. For many decades, ...

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

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.