PIpepTolDC Starts A Phase-I Clinical Trial
joshua levy
The idea behind this research is to remove dendritic cells from a person with T1D, grow them out with vitamin D3 and a fragment of
proinsulin (C19-A3), and then put them back into the same person they came from. The goal of this therapy is to teach the immune system to stop attacking the beta
cells.
Proinsulin is a molecule that the body makes as part of the process of making insulin. The body makes proinsulin first, and then (near the end of the process), coverts the proinsulin to insulin. Proinsulin is a target of the immune system's mistaken attack on beta cells, so teaching the immune system that proinsulin is a normal part of the body might cure (or help to cure) T1D.
Dendritic cells are part of the immune system which find foreign cells and "present" them to T-cells (another part of the immune system) so that the T-cells know what to attack. You can read more about them here: http://en.wikipedia.org/wiki/Dendritic_cells.
Although this research is unique, it combines two parts which have each been used before. Modifying dendritic cells has been done in the past by Trucco (late 2000s) and DiaVacs (early 2010s). Both groups were removing dendritic cells, treating/growing them, and then putting them back, just as done here. The difference between all these lines of research was how the cells were treated while they were being grown outside the body.
Similarly, proinsulin (C19-A3) has been a focus of research by a group at Cardiff for over 10 years. However, they are testing a direct injection of proinsulin, not using it to train dendritic cells outside the body, as done here.
The Study
This is a phase-I study, enrolling 7 people, all of whom will get treated. There is no control group. The seven patients will be adults who were diagnosed between 1 and 4 years previously, so these are not honeymooners, they have established type-1 diabetes. Each patient will receive two doses of the expanded dentritic cells, a month apart, and then be followed for two years.
The study has a total of five primary end points. Some of these are safety related, and others measure the effects of the treatment (ie. how it effects the immune system). There are also nine secondary end points, which measure effectiveness and more effects in the immune system.
This study is recruiting now and they hope to finish by October 10, 2022. They are recruiting here:
City of Hope Medical Center, Duarte, California, United States, 91010
Contact: Ryotaro Nakamura 866-444-7538 DL-T...@coh.org
This study is being funded by The Wanek Family Project.
Discussion
The researchers describe this as a "vaccine" or a "reverse vaccine", but most people would not consider it a vaccine at all. Calling it a "reverse vaccine" is closer to how most people would think of this treatment. A classic vaccine preps the body to fight off a disease. It teaches the body about the disease ahead of time, so the body can stage a strong battle at the first sign of infection. This treatment does the opposite. It teaches the body not to attack something. In some ways, it is similar to shots people sometimes get to lessen allergies. (Although I want to emphasize that T1D is not a classic allergy.) But in any case, I think it is a mistake to think of this as being like a classic vaccine.
Although this is a phase-I trial, it is not the first time this treatment has been tested. It was previously tested in Europe. This study gave three different doses to three people each (no control group). Safety and feasibility data was good, but no
effectiveness results were seen. You can read the journal article here:
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30104-2/fulltext
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT04590872