ProTcell platform
Smart Immune is developing ProTcell: a pioneering, allogeneic, T-cell therapy platform empowered by the thymus that rapidly rearms the immune system to fight cancers and infections
A 7-day cell culture process to differentiate blood stem cells into T-cell progenitors under GMP conditions via our patented ex vivo lymphoid niche technology
Significant T-cell progenitor yields owing to a robust and scalable proprietary bioproduction process
T-cell progenitors that migrate directly to the thymus and are educated to kill 200 million enemies like pathogens and tumors
Immune impairment is a large unmet medical need
50 000 immune-compromised patients have to live in EU/US with life-threatening cancers and infections. They require allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) which is held back by:
• High costs & poor benefit/risk
• Donor matching
• Lengthy process to immune recover leading to a long period of vulnerability
• Complex treatments requiring highly skilled staff & integrated centers with GMP facilities
• Infection, relapse or rejection of the graft
We developed a unique bioproduction process to grow a new type of white blood cell ex vivo – T-cell progenitors originating from blood stem cells – in 7 days rather than the 15 months needed in normal physiology.
When infused into the patient, our T-cell progenitors, so called ProTcells, migrate to the thymus, a key organ of the lymphoid system. There, they are selected, educated and differentiated to become mature T-cells able to identify the difference between self and around 200 million pathogens and tumors − the full immune system repertoire required to fight life-threatening diseases.
In the patient's thymus, the ProTcells acquire all the characteristics of the patient's natural cells, becoming similar to them in every way. Thus, they present no risk of rejection for the patients and remain active for many years.
Smart Immune’s T-cell progenitors can also be armed with chimeric antigen receptors (CAR) or recombinant T-cell receptors (rTCR) to target specific tumour antigens. In an allogeneic setting, the risk of GvHD is dramatically reduced owing to the negative selection of T-cells during their maturation in the thymus.
Non-clinical publications
Manufacturing of Human T-lymphoid Progenitors from Two Different Hematopoietic Stem Cell Sources and Perspective for New Immunotherapies. Gaudeaux P, Moirangthem RD, Rault P, Sadek H, Carbone F, Lavaert M, et al. , J Cell Immunol. 2022;4(4):149-157.
A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors.
Moirangthem RD, Ma K, Lizot S, Cordesse A, Olivré J, de Chappedelaine C, Joshi A, Cieslak A, Tchen J, Cagnard N, Asnafi V, Rausell A, Simons L, Zuber J,Taghon T, Staal F, Pflumio F, Six E, Cavazzana M, Lagresle-Peyrou L, Soheili T and André I.
Cell Mol Immunol (2021)18:1662–1676. doi: 10.1038/s41423-021-00706-8.
A human postnatal lymphoid progenitor capable of circulating and seeding the thymus.
Six EM, Bonhomme D, Monteiro M, Beldjord K, Jurkowska M, Cordier-Garcia C, Garrigue A, Dal Cortivo L, Rocha B, Fischer A, Cavazzana-Calvo M, André-Schmutz I. J Exp Med. 2007 Dec 24;204(13):3085-93. Epub 2007 Dec 10.
Notch ligands Delta and lymphoid development niches.
Six E, André Schmutz I, Cavazzana-Calvo M.
Med Sci (Paris). 2007 Jan;23(1):21-4. French. No abstract available.
Human T-lymphoid progenitors generated in a feeder-cell-free Delta-like-4 culture system promote T-cell reconstitution in NOD/SCID/γc(-/-) mice.
Reimann C, Six E, Dal-Cortivo L, Schiavo A, Appourchaux K, Lagresle-Peyrou C, de Chappedelaine C, Ternaux B, Coulombel L, Beldjord K, Cavazzana-Calvo M, Andre-Schmutz I. Stem Cells. 2012 Aug;30(8):1771-80. doi: 10.1002/stem.1145.
Generation of adult human T-cell progenitors for immunotherapeutic applications.
Simons L, Ma K, de Chappedelaine C, Moiranghtem RD, Elkaim E, Olivré J, Susini S, Appourchaux K, Reimann C, Sadek H, Pellé O, Cagnard N, Magrin E, Lagresle-Peyrou C, Taghon T, Rausell A, Cavazzana M, André-Schmutz I.
J Allergy Clin Immunol. 2018 Apr;141(4):1491-1494.e4. doi: 10.1016/j.jaci.2017.10.034. Epub 2017 Dec 5. No abstract available.
Clinical publications
T-lymphoid progenitor-based immunotherapies: clinical perspectives for one and all. Gaudeaux, P., Moirangthem, R.D., Paillet, J. et al. Cell Mol Immunol (2022). https://doi.org/10.1038/s41423-022-00927-5
Ex vivo generated human T-lymphoid progenitors as a tool to accelerate immune reconstitution after partially HLA compatible hematopoietic stem cell transplantation or after gene therapy.
André I, Simons L, Ma K, Moirangthem RD, Diana JS, Magrin E, Couzin C, Magnani A, Cavazzana M., Bone Marrow Transplant. 2019 Aug;54(Suppl 2):749-755. doi: 10.1038/s41409-019-0599-9. Review.
Concise Review: Boosting T-Cell Reconstitution Following Allogeneic Transplantation-Current Concepts and Future Perspectives.
Simons L, Cavazzana M, André I., Stem Cells Transl Med. 2019 Jul;8(7):650-657. doi: 10.1002/sctm.18-0248. Epub 2019 Mar 18. Review.
Advances in adoptive immunotherapy to accelerate T-cellular immune reconstitution after HLA-incompatible hematopoietic stem cell transplantation.
Reimann C, Dal Cortivo L, Hacein-Bey-Abina S, Fischer A, André-Schmutz I, Cavazzana-Calvo M., Immunotherapy. 2010 Jul;2(4):481-96. doi: 10.2217/imt.10.36. Review.