New immun­o­ther­apies from induced stem cells

ISAR Bioscience aims to teach iPS cells how to fight autoim­mune dis­eases and can­cer in an effect­ive and sus­tained manner.

To com­bat autoim­mune dis­eases effi­ciently, ISAR Bioscience pro­duces vari­ous types of immune cells from human induced pluri­po­tent stem cells (hiPSC). Pro­duced under good man­u­fac­tur­ing prac­tice (GMP) con­di­tions, they are inten­ded for allo­gen­eic cell ther­apies. This means that they should be avail­able at short notice and not have to be pro­duced from a patient’s own immune cells in a com­plex pro­cess (as is cur­rently necessary).
These cells must be “taught” how to effect­ively com­bat the dis­ease-caus­ing cells in autoim­mune dis­eases (or also can­cer). To achieve this, they are equipped with arti­fi­cial recept­ors called chi­meric anti­gen recept­ors (CARs) via gen­ome edit­ing. ISAR Bioscience is devel­op­ing vari­ous types of CARs for this purpose.
Spe­cial types of CARs are being developed to com­bat autoim­mune dis­eases: these are termed chi­meric auto-anti­gen recept­ors (CAARs). The second A in this abbre­vi­ation stands for auto-anti­gen: these are pro­teins of the body that are attacked by the immune sys­tem in such dis­eases. At ISAR Bioscience, we want to use CAAR-equipped immune cells to sup­press this attack.
As a first example of an autoim­mune dis­ease, we are devel­op­ing a CAAR for the treat­ment of a thyroid dis­ease triggered by autoantibod­ies, which can be severe in many patients (Graves’ dis­ease) and can also spread to the eyes (endo­crine or Graves’ orbit­o­pathy). Other autoim­mune dis­eases, such as rheum­at­oid arth­ritis, are to follow.
To this end, stem cells are mod­i­fied by gen­ome edit­ing so that they can pro­duce a CAAR. They are then used to per­man­ently gen­er­ate thera­peutic “ready-to-fight” immune cells. The new plat­form allows the serial pro­duc­tion of stand­ard­ized CAAR cell batches that can be used repeatedly.
The reg­u­lat­ory author­ity for such ther­apies, the Paul Ehr­lich Insti­tute, con­siders the pro­ced­ure to be prom­ising and has given ISAR Bioscience the green light for fur­ther devel­op­ment. The pos­it­ive eval­u­ation was accom­pan­ied by the defin­i­tion of spe­cific­a­tions for the man­u­fac­ture and approval of a cell bank for pro­duc­tion in accord­ance with good man­u­fac­tur­ing prac­tice (GMP). Fur­ther pre­clin­ical stud­ies and tox­ic­o­lo­gical tests are in pre­par­a­tion so that clin­ical tri­als of the novel cell ther­apy in humans can begin as soon as possible.

Pat­ent

Ammon T, Rabea Hein R, Hans-Peter Holthoff HP, Martin Ungerer M (2024). Chi­meric autoanti­gen receptor for treat­ing autoim­mune dis­ease. Pat­ent applic­a­tion EP24173058.9

Pub­lic­a­tions on this topic