ProTcell Platform
Smart Immune is developing ProTcell: a pioneering, allogeneic,thymus-empowered T-cell therapy platform. ProTcell reinvigorates the thymus by introducing healthy allogeneic T-cell progenitors into the patient, which then develop into a full immune repertoire – an ‘off the shelf’ product for personalised medicine.
Smart Immune has replicated a human lymphoid niche ex vivo using its knowledge of CD34+ T cell differentiation.
A thymus-homing capability of unique T-cell progenitors so called ProTcell at the earliest point of lineage commitment.
A great capability of ProTcell to differentiate ex vivo in NK cells.
The ability to culture and expand such short-lived, fragile, unique T-cells populations in GMP conditions, using proprietary Notch ligand SIFP3.
Smart Immune develops large numbers of these T-cell progenitors from hematopoietic stem cells in one week ex vivo, rather than the one year it takes inside the body. The thymus then ‘educates’ these T-cell progenitors to become the complete repertoire of immune cells in around three months, compared with 15-18 months through bone marrow transplantation alone, significantly reducing the time to full immune recovery and providing a transformational shift in the benefit/risk ratio of allogeneic T-cell medicine.
The ProTcell can be used with or without CAR/TCR transduction giving rise, when infused to patients, to the first long lasting cell therapy drug product, significantly improving the clinical outcome for the patients.
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.