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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Project ACT (Automated autologous cell therapy system)

Teaser

Summary

Among all cancers, metastatic melanoma (MM) represents one of the major health problems. MM is notorious for affecting young and middle-aged people, results in 66000 related deaths yearly worldwide and therefore has a large impact on years of healthy life lost.
Recently, promising results of autologous cell therapy (ACT) have shown that up to 20% of patients can be cured with one single course of this immunotherapy. The resulting survival rates of patients treated confirm this approach as being among the most efficient therapies available. The only treatment with comparable response rates of long durability is the combination of two products, ipilimumab and nivolumab. The mean treatment time is eight months compared with one week ACT treatment with T-cells.
Further, the treatment with ipilimumab and nivolumab increased the serious adverse events by 62%.
It is expected that it will be sold at high price (currently, treatment with each of the single agents costs over 100 000 â‚¬/year per patient). This cost will create a large burden on society and a large saving could be obtain if the <100,000â‚¬ could be substituted by an ACT treatment 24.000â‚¬.
The ACT treatment has been conducted in several small pilot studies with over 1.000 patients treated worldwide; however none of these trials have included enough patients to be approved by neither European Medicines Agency (EMA) nor FDA.
The current ACT method can only be conducted at hospitals with sterile GMP facilities. Further, TIL production for ACT is labor intensive and must be performed at hospitals with a sterile clean room. This limits the use of this new and efficient cancer treatment to a few highly specialized hospitals. The objective of this application is to develop a dedicated bioreactor that will enable the treatment to be used on an extended number of hospitals. And importantly, this novel treatment has the potential to be expanded to the treatment of other cancer types this will enable the clinicians to conduct at study with appropriate number of patients to be approved by EMA/FDA. The commercial potential for ACT is estimated to be more than 4 Billion $ per year.
In this project we have conducted test that clearly support that the proposed device design is indeed cable of preparing ACT in a closed system.

Work performed

T-cell expansion is currently performed in a sterile facility in 3 different processes. Each of the 3 processes are performed in different containers. The main objective of this research was to verify that the 3 steps in T-cell expansion can be performed in an inventive closed device system.

1. Rapid Expansion Protocol (REP)
The patients cells needs to be activated by the feeder cells and to allow this interaction the cells must be located close to each other in order to allow the patient t cell to be activated by the cytokines (Growth factors etc.) from the feeder cells. Gentle stirring every 6 hours may improve the expansion as new cell-cell interaction may be accomplished by gentle stirring.

2. Perfusion
In this phase the cells need to have access to energy and oxygen. Gentle agitation that distribute oxygen in the fluid/medium and to uptake new oxygen is important. However T-cells tend to aggregate if stirring is too aggressive like standard mechanical propelling.

3. Harvesting and purifying the cells
By gravity centrifugation the cells can be compacted as the density of the cells are higher than the fluid. After compaction, excess fluid/medium can be removed. Then new saline/medium can be added and the process repeated until the cells are in pure saline/medium.

In this project, we have conducted test that clearly support that the proposed device design is capable of performing all 3 steps in a closed system.

Final results

In this project we have conducted test that clearly support that the proposed device design is indeed cable of preparing ACT in a closed system that will result in the possibility to make more uniform cell treatment to occur in more hospitals.