IMMUNOSTEM technology refers to using a virus (specifically a lentivirus) to deliver a new gene into cells, which will then produce a specific protein PD-L1 (Programmed Death-Ligand 1). This protein plays a key role in the immune system by telling T-cells not to attack a specific other cell (in this case, beta cells). This is done to the patient's own blood. It is removed, treated in this way, and then put back, thereby treating the T-cells in the blood so they will not attack beta cells.
Digression: this whole area of research was motivated by cancer. The PD-L1 protein is hijacked by cancer cells to help them hide from the immune system. By genetically engineering cells to produce human PD-L1, scientists can research this process. But the researchers for this study hope to use this mechanism to protect beta cells from the autoimmune attack that starts T1D.
The PD-L1 overexpression technology licensed by Altheia Science was developed by researchers who later co-founded the company. Alessandra Biffi and Paolo Fiorina did this work at Boston Children's Hospital.
To create the IMMUNOSTEM treatment, specific blood cells from a patient are collected through a procedure called leukapheresis. These collected cells are then genetically engineered using a modified virus, the PD-L1 lentiviral vector, to carry new genetic instructions. These instructions enable the cells to produce the PD-L1 protein. After modification, the cells are frozen and later re-infused into the patient's bloodstream as a single injection.
This Clinical Trial
This trial is a Phase I study where everyone gets the treatment, meaning there is no placebo group and no randomization. All 15 people will receive treatment. They will all be honeymoon adults (aged 18 to 40), within 180 days of diagnosis.
Patients will get one infusion and have follow-up for 24 months. The primary endpoint of this Phase I study is safety, but secondary endpoints will evaluate the early efficacy of the treatment, especially c-peptide levels, as well as management issues like blood glucose levels, insulin requirements, A1c numbers, etc.
This study is being done at one site in Italy. Contact info is:
Name: Paolo Rizzardi, MD
Phone Number: +39 335 1935042
Email: paolo.rizzardi@altheiascience.com
Location: Padua, Italia, Italy, Azienda Ospedale-Università Padova
Discussion
Since this is a new type of gene therapy (for T1D), there are two new risks involved. One is infusing the new cells, and the other is using the virus to genetically modify them ahead of time. However, the cell infusion has been done for decades for treating cancer, and is considered safe in that context.
The other new (to T1D) risk is the use of a lentivirus to directly modify a cell's DNA to produce PD-L1. It is not currently in use as an FDA approved treatment for any disease. Both gene therapy and lentiviral vectors have approved uses for other conditions, but not to produce PD-L1 as used here.
Altheia Science is focused on applying PD-L1 technology to type 1 diabetes, but is also working on using it to treat Multiple Sclerosis, another autoimmune disease.
A study published in November 2024 by these researchers showed that a PD-L1 based treatment resulted in NOD mice stabilizing with a BG level of 150-300, while those untreated did not stabilize below 600 (when it could no longer be measured).
Previous Research Publication: https://pubmed.ncbi.nlm.nih.gov/29141886
Previous Research Publication: https://pubmed.ncbi.nlm.nih.gov/29141886
As far as I know, this is the only research attacking T1D using this PD-L1 approach, but there has been several successes in using lentivirus to inject DNA in the past for a variety of rare genetic diseases: β-thalassemia, X-linked adrenoleukodystrophy, metachromatic leukodystrophy, and Wiskott-Aldrich Syndrome.
For More Information
- Company: https://www.altheiascience.com
- Clinical Trial Registery: https://clinicaltrials.gov/study/NCT06938334
- Researchers' Study Explanation: https://www.altheiascience.com/immunostem
Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!
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