For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells.
The process is quick and effective, representing a pioneering contribution for applying direct reprogramming for inducing immunity. Importantly, the finding opens up the possibility of developing novel dendritic cell-based immunotherapies against cancer.
Our so-called dendritic cells function as the immune system’s sentinels. Their task is to scan our tissues for foreign particles, such as bacteria, viruses or cancer cells, and to devour them. They subsequently break down the particles into smaller pieces, known as antigens, and present them on the surface to the immune system’s killer cells (T-cells). In this way, the killer cells learn which infectious agents and cancer cells they are to search for and kill.
Due to these key features, dendritic cell-based strategies have been tested to treat cancer patients. However, cancer can affect the dendritic cells in such a way that they get lost or become dysfunctional. We therefore need to find new ways of generating dendritic cells for every patient. Now, for the first time, a research team in Lund has succeeded in obtaining dendritic cells by a process called direct reprogramming. They have identified three essential proteins (PU.1, IRF8 and BATF3) that are required and sufficient to change the identity of mouse cells to make them become dendritic cells instead. They have also confirmed that the same protein cocktail reprograms human skin-derived cells to dendritic cells. This study is now published and highlighted in the cover of the journal Science Immunology.
“From a tissue section taken from the skin, we can cultivate millions of cells and reprogram them to dendritic cells in a process that takes only nine days”, says Filipe Pereira, the leader of the research team that conducted the study.
“Our study has shown that reprogrammed cells have the ability to effectively capture and present antigens to killer cells in the same way as ‘natural’ dendritic cells.” The researchers can even direct the induced dendritic cells towards a particular target by presenting the right antigen to them in a test tube, before introducing the cells into the organism. This finding opens up future possibilities to develop new strategies for immunotherapy against solid tumours and blood cancers, beyond the treatments currently available.
“This represents an excellent opportunity to merge the fields of cellular reprogramming and cancer immunotherapy. Generating dendritic cells employing direct cell reprogramming is very attractive from a therapeutic perspective: our studies may be useful in the clinic for generation of patient-specific dendritic cells”, according to Filipe Pereira.
Cancer immunotherapy employs the cellular components of a persons’ immune system to fight cancer and it was awarded with the Nobel Prize in Physiology or Medicine this year. By using reprogrammed dendritic cells the probability of rejection by the organism is lower as these cells can be generated from the skin of each individual patient.
“Tumours often undergo a number of mutations, developing into a heterogeneous entity, which makes it more difficult for the immune system to identify them as a threat. In a more creative perspective, we now want to explore the process of dendritic cell reprogramming to develop a cancer gene therapy. We are aiming at injecting the three reprogramming proteins straight into the tumour forcing it to present their own tumour-specific antigens. This allows the activation of the killer cells against tumour cells and may lead to their elimination. We have named this concept TrojanDC in an analogy with Homero’s Trojan horse. The great potential of this technology for cancer treatment lead us to start a new company together with Lund University for the development of this concept into a product that hopefully will reach cancer patients one day”, says Filipe Pereira.
“Additionally, our studies open up the possibility of reprogramming other dendritic cell sub-types taking advantage of their distinct functional features. A better understanding of the mechanisms that determine the identity of immune sentinels and of how to use this knowledge to reprogram other cell types into dendritic cells could make these patient-specific cells useful in the clinic”, concludes Filipe Pereira.
Learn more: WATCH: A code for reprogramming immune sentinels
The Latest on: Immunotherapies
via Google News
The Latest on: Immunotherapies
- Imugene’s gastric cancer drug clears first safety hurdles on December 16, 2018 at 4:57 pm
It is developing a suite of immunotherapies that seek to activate the immune system in cancer sufferers to treat and eradicate tumours. And it has now passed the first clinical trial hurdle, with its ... […]
- The immune system's supercell -- how it matures on December 15, 2018 at 2:02 pm
Now scientists have mapped how the different steps of the maturation process of these supercells from blood producing stem cells in the bone marrow are regulated: knowledge which is crucial for the de... […]
- Amgen's BiTE Immunotherapies Show Promise in Early Studies on December 14, 2018 at 10:45 pm
Amgen Inc. AMGN announced first clinical data from the early-stage studies on its two investigational novel bispecific T cell engager (BiTE) immunotherapies — AMG 420 and AMG 330. Two separate ... […]
- New findings could help develop new immunotherapies against cancer on December 13, 2018 at 10:53 pm
NK cells, or natural killer cells, play an important role in the body's defences against cancer and various infections. Now, in a joint project, researchers at Lund University in Sweden, the Universit... […]
- Combined immunotherapies – potential and pitfalls on December 12, 2018 at 4:05 pm
‘Combining therapeutic compounds is the first logical step towards better results, namely higher rates of patients responding to treatment, with deeper and more sustained responses’ Immunotherapies ha... […]
- Global Allergy Immunotherapies Markets to 2023 with ALK, Allergy Therapeutics, HAL Allergy, Merck, and Stallergenes Greer Leading the Competition on December 7, 2018 at 9:34 am
The "Global Allergy Immunotherapies Market 2019-2023" report has been added to ResearchAndMarkets.com's offering. The allergy immunotherapies market is forecast register a CAGR of more than 7% by ... […]
- Global Allergy Immunotherapies Market Analysis & Forecast 2019-2023: The Increasing Prevalence of Various Types of Allergies is Augmenting Growth (Over 7%) - ResearchAndMarkets.com on December 6, 2018 at 7:52 am
The latest trend gaining momentum in the market is the emerging drug development technologies. According to the report, one of the major drivers for this market is the increasing prevalence of various ... […]
- Cancer biotech Synthorx prices upsized IPO at $11 midpoint on December 6, 2018 at 6:13 am
Synthorx, a preclinical biotech developing immunotherapies for solid tumors, raised $131 million by offering 11.9 million shares at $11, the midpoint of the $10 to $12 range. The company offered addit... […]
- The Allergy Immunotherapies Market will register a CAGR of more than 7% by 2023 on December 5, 2018 at 2:26 pm
The emerging drug development technologies is likely to help the market grow during the forecast period. The recent advances in the immunotherapy drug development are helping the pharmaceutical compan... […]
via Bing News