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
- HCW Biologics Showcases Scientific Paper in Molecular Therapy Highlighting Potential of HCW9218 ...on August 24, 2021 at 4:32 am
Lead Drug Candidate Engineered UsingTissue FactOr-Based FusIon (TOBI™) Platform Preclinical Data Demonstrated HCW9218 Antitumor Activity as Single-Agent Monotherapy and as an Adjunct to Enhance ...
- ASX Announcement: AdAlta and Carina Biotech to develop next-generation CAR-T cancer therapeuticson August 24, 2021 at 4:22 am
AdAlta Limited (ASX:1AD) and Carina Biotech Pty Ltd have entered a collaboration agreement to develop next-generation i-body enabled CAR-T cells, with the potential to bring CAR-T cell therapy to ...
- Immunocore Announces that U.S. Food and Drug Administration and European Medicines Agency ...on August 24, 2021 at 4:02 am
Immunocore Announces that U.S. Food and Drug Administration and European Medicines Agency accept Biologics License Application and Marketing Authorization Application for Tebentafusp in Metastatic ...
- Umoja Biopharma Appoints Greg Sargen to its Board of Directorson August 24, 2021 at 4:00 am
Umoja Biopharma, an oncology company leveraging its proprietary integrated technologies to reprogram immune cells in vivo to ...
- Pfizer makes big move in blood cancers with $2.3B Trillium acquisitionon August 23, 2021 at 2:59 pm
Though Gilead Sciences leads the group of companies developing immunotherapies that target the cancer protein CD47, Pfizer contends that molecules it is getting through the Trillium Therapeutics ...
- Up-and-Coming Immunotherapies Target Aβ and Tauon August 19, 2021 at 5:00 pm
While aducanumab, donanemab, and lecanemab are approved or inching closer to it, the next generation of immunotherapies moves through the ranks. At AAIC, scientists presented preclinical data on both ...
- Marker Therapeutics Awarded $13.1 Million Grant from the Cancer Prevention and Research Institute of Texason August 19, 2021 at 1:05 pm
Marker Therapeutics, Inc. (Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological mal ...
- Bolt Biotherapeutics: Pioneering A New Class Of Immunotherapieson August 18, 2021 at 3:42 pm
Bolt has built out an immunotherapy platform to design biologics for cancers that are not accessible for the current standard-of-care. Find out if the stock is a buy.
- Cancer Immunotherapies Market Size Analysis, Industry Outlook, Regional Forecast 2021-2027| Amgen, AstraZeneca, Roche, Bristol-Myers Squibbon August 17, 2021 at 7:17 am
Top Key Players Included in Cancer Immunotherapies Market Report: Amgen, AstraZeneca, Roche, Bristol-Myers Squibb, Bayer, Merck, ARMO BioSciences (Eli Lilly), Novartis, Pfizer, Johnson & Johnson, ...
via Bing News