The cause of the development and progression of T1DM is an autoimmune process in which the patient’s altered immune system destroys its own β-cells. However, it is possible to protect β-cells from destruction if the aggressive immune response is halted.

It is currently impossible to completely cure T1DM, but it is possible to significantly improve the patient’s quality of life by halting the immune system’s «aggressive behavior» through immunotherapy. Even with the death of 90% of all pancreatic β-cells, the remaining 10% can compensate for the insulin production deficit.

Specific immunotherapy for T1DM utilizes the properties of DCs, which are key regulators of immune responses in humans. By presenting various antigens to T-lymphocytes, DCs can either initiate or suppress an immune response.

Specifically, tolDCs possess immunosuppressive properties, bringing the immune system into an anti-inflammatory state tolerant to autoantigens. Specially prepared tolDCs are capable of suppressing the autoimmune response against β-cells in patients with T1DM.

Cellular immunotherapy for T1DM is based on the use of the patient’s own tolDCs, programmed to suppress the autoimmune response against β-cells.

As a result of this therapy, the number of autoantibodies to β-cell antigens and the activity of autoantigen-specific Tcells decrease, thereby increasing the survival rate of β-cells and restoring their insulinproducing capability. Additionally, other inflammatory processes associated with T1DM are reduced.

Treatment Scheme

The cell therapy method is indicated for patients with T1DM older than 18 years, where laboratory research results determine its clinical feasibility, and is based on the use of BMCP based on tolDCs.

Each therapeutic dose of BMCP contains at least 1 million live tolDCs derived from the patient’s biomaterial and «specially prepared» in the laboratory — priming with a pool of GAD65 antigen peptides and co-culturing with mesenchymal stem cells.

Stages of Cell Therapy (Outpatient):

• Day 1 — Collection of patient biomaterial (peripheral venous blood) in the amount of 50-100 ml, immunostatus assessment
• Day 2-7 — Production of tolDCs in the laboratory, BMCP quality control
• Day 9 — Subcutaneous administration of BMCP

The cell therapy course involves 5 BMCP injections with an interval of 1-1.5 months.

Since blood monocytes are the source of tolDCs, their low content in the blood (less than 100 per 1 μl) will result in a low number of tolDCs. Therefore, a complete blood count with an absolute monocyte count is performed before each biomaterial collection.

BMCP administration is performed in a procedural office via subcutaneous injection after a skin test. After the procedure, the patient is observed in a day hospital ward for 1 hour.

Effectiveness

Suppressing the autoimmune process, unfortunately, does not lead to β-cell regeneration and increase. Therefore, the prognosis for immunotherapy efficacy largely depends on the remaining β-cell reserve at the start of treatment.

To assess this functional potential (preserved secretion), a mandatory laboratory test is performed to determine the Cpeptide level in the blood serum.

The clinical effect of the cell therapy course is manifested by stabilizing diabetes progression, in particular, the absence of disease progression based on laboratory parameters, including the absence of a need to increase the daily insulin dose.

The maximum clinical effect can be expected with continuous cell therapy courses under the control of peripheral blood autoantigen-specific T-cells and/or autoantibodies to β-cell antigens (GAD65).

Cellular therapy significantly impacts the prevention of T1DM complications, significantly reducing the risk of target organ damage: kidneys, cardiovascular system, and retinal damage.

However, complete recovery cannot be expected. Clinical efficacy assessment is based on the results of general clinical examination, daily glycemic parameters, HbAlc levels, basal and stimulated (standard breakfast) C-peptide levels, autoantibody levels to β-cell components, and quality of life assessment.

Follow-up laboratory examination is recommended 3 and 6 months after the end of the cell immunotherapy course.

Safety and Complications

It has been proven that the use of autologous (i.e., the patient’s own) tolDCs is well tolerated by the patient and completely safe, causing no allergic, toxic reactions, does not suppress overall immunity, and does not stimulate tumor development.

Despite comprehensive complication prevention implemented by medical personnel, blood collection may cause reactions such as: bruising at the collection site, inflammation of the punctured vein, allergic reactions to the antiseptic used for skin treatment.

Subcutaneous tolDC administration may be accompanied by a short-term (1-2 days) fever up to 38°C, redness, and swelling at the injection site, which do not require medical intervention and resolve on their own.