Jorge Mansilla-Soto, PhD
Jorge Mansilla-Soto, PhD
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Overview
Immunobiology of engineered CAR T cells
Associations
- Immunology
- Blood and Marrow Transplant and Cellular Immunotherapy
- Immuno-Oncology Program
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Research Interest
Our general research interest is the understanding of how engineered CAR receptors modulate T cell function in response to tumor targets. Using locus-specific human CAR T cells, we study how distinct chimeric receptor designs drive T cell anti-tumor activity in response to tumor targets in both hematological and solid tumor animal models. In addition, we study the signaling and transcriptional programs that are established in diverse stimulation environments with the ultimate goal to leverage this information to design more efficacious T cell therapies for cancer.
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Publications
- Haubner S, Mansilla-Soto J, Nataraj S, Kogel F, Chang Q, de Stanchina E, Lopez M, Ng MR, Fraser K, Subklewe M, Park JH, Wang X, Rivière I, Sadelain M. Cooperative CAR targeting to selectively eliminate AML and minimize escape. Cancer Cell. 2023 Nov.41(11):1871-1891.e6. Pubmedid: 37802054.
- Jain N, Zhao Z, Feucht J, Koche R, Iyer A, Dobrin A, Mansilla-Soto J, Yang J, Zhan Y, Lopez M, Gunset G, Sadelain M. TET2 guards against unchecked BATF3-induced CAR T cell expansion. Nature. 2023 Mar.615(7951):315-322. Pubmedid: 36755094. Pmcid: PMC10511001.
- He C, Mansilla-Soto J, Khanra N, Hamieh M, Bustos V, Paquette AJ, Garcia Angus A, Shore DM, Rice WJ, Khelashvili G, Sadelain M, Meyerson JR. CD19 CAR antigen engagement mechanisms and affinity tuning. Sci Immunol. 2023 Mar.8(81):eadf1426. Pubmedid: 36867678. Pmcid: PMC10228544.
- Odak A, Yuan H, Feucht J, Cantu VA, Mansilla-Soto J, Kogel F, Eyquem J, Everett J, Bushman FD, Leslie CS, Sadelain M. Novel extragenic genomic safe harbors for precise therapeutic T-cell engineering. Blood. 2023 Jun.141(22):2698-2712. Pubmedid: 36745870. Pmcid: PMC10273162.
- Chow A, Uddin FZ, Liu M, Dobrin A, Nabet BY, Mangarin L, Lavin Y, Rizvi H, Tischfield SE, Quintanal-Villalonga A, Chan JM, Shah N, Allaj V, Manoj P, Mattar M, Meneses M, Landau R, Ward M, Kulick A, Kwong C, Wierzbicki M, Yavner J, Egger J, Chavan SS, Farillas A, Holland A, Sridhar H, Ciampricotti M, Hirschhorn D, Guan X, Richards AL, Heller G, Mansilla-Soto J, Sadelain M, Klebanoff CA, Hellmann MD, Sen T, de Stanchina E, Wolchok JD, Merghoub T, Rudin CM. The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer. Immunity. 2023 Jan.56(1):93-106.e6. Pubmedid: 36574773. Pmcid: PMC9887636.
- Hamieh M, Mansilla-Soto J, Rivière I, Sadelain M. Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating. Cancer Discov. 2023 Apr.13(4):829-843. Pubmedid: 36961206. Pmcid: PMC10068450.
- van der Stegen SJC, Lindenbergh PL, Petrovic RM, Xie H, Diop MP, Alexeeva V, Shi Y, Mansilla-Soto J, Hamieh M, Eyquem J, Cabriolu A, Wang X, Abujarour R, Lee T, Clarke R, Valamehr B, Themeli M, Riviere I, Sadelain M. Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells. Nat Biomed Eng. 2022 Nov.6(11):1284-1297. Pubmedid: 35941192. Pmcid: PMC9669107.
- Boulad F, Maggio A, Wang X, Moi P, Acuto S, Kogel F, Takpradit C, Prockop S, Mansilla-Soto J, Cabriolu A, Odak A, Qu J, Thummar K, Du F, Shen L, Raso S, Barone R, Di Maggio R, Pitrolo L, Giambona A, Mingoia M, Everett JK, Hokama P, Roche AM, Cantu VA, Adhikari H, Reddy S, Bouhassira E, Mohandas N, Bushman FD, Rivière I, Sadelain M. Lentiviral globin gene therapy with reduced-intensity conditioning in adults with β-thalassemia: a phase 1 trial. Nat Med. 2022 Jan.28(1):63-70. Pubmedid: 34980909. Pmcid: PMC9380046.
- Mansilla-Soto J, Eyquem J, Haubner S, Hamieh M, Feucht J, Paillon N, Zucchetti AE, Li Z, Sjöstrand M, Lindenbergh PL, Saetersmoen M, Dobrin A, Maurin M, Iyer A, Garcia Angus A, Miele MM, Zhao Z, Giavridis T, van der Stegen SJC, Tamzalit F, Rivière I, Huse M, Hendrickson RC, Hivroz C, Sadelain M. HLA-independent T cell receptors for targeting tumors with low antigen density. Nat Med. 2022 Feb.28(2):345-352. Pubmedid: 35027758. Pmcid: PMC9469647.
- Katsarou A, Sjöstrand M, Naik J, Mansilla-Soto J, Kefala D, Kladis G, Nianias A, Ruiter R, Poels R, Sarkar I, Patankar YR, Merino E, Reijmers RM, Frerichs KA, Yuan H, de Bruijn J, Stroopinsky D, Avigan D, van de Donk NWCJ, Zweegman S, Mutis T, Sadelain M, Groen RWJ, Themeli M. Combining a CAR and a chimeric costimulatory receptor enhances T cell sensitivity to low antigen density and promotes persistence. Sci Transl Med. 2021 Dec.13(623):eabh1962. Pubmedid: 34878825. Pmcid: PMC9869449.
- Amor C, Feucht J, Leibold J, Ho YJ, Zhu C, Alonso-Curbelo D, Mansilla-Soto J, Boyer JA, Li X, Giavridis T, Kulick A, Houlihan S, Peerschke E, Friedman SL, Ponomarev V, Piersigilli A, Sadelain M, Lowe SW. Senolytic CAR T cells reverse senescence-associated pathologies. Nature. 2020 Jul.583(7814):127-132. Pubmedid: 32555459. Pmcid: PMC7583560.
- Hamieh M, Dobrin A, Cabriolu A, van der Stegen SJC, Giavridis T, Mansilla-Soto J, Eyquem J, Zhao Z, Whitlock BM, Miele MM, Li Z, Cunanan KM, Huse M, Hendrickson RC, Wang X, Rivière I, Sadelain M. CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature. 2019 Apr.568(7750):112-116. Pubmedid: 30918399. Pmcid: PMC6707377.
- Boulad F, Mansilla-Soto J, Cabriolu A, Rivière I, Sadelain M. Gene Therapy and Genome Editing. Hematol Oncol Clin North Am. 2018 Apr.32(2):329-342. Pubmedid: 29458735.
- Perna F, Berman SH, Soni RK, Mansilla-Soto J, Eyquem J, Hamieh M, Hendrickson RC, Brennan CW, Sadelain M. Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML. Cancer Cell. 2017 Oct.32(4):506-519.e5. Pubmedid: 29017060. Pmcid: PMC7025434.
- Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, Odak A, Gönen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017 Mar.543(7643):113-117. Pubmedid: 28225754. Pmcid: PMC5558614.
- Seyffert M, Glauser DL, Schraner EM, de Oliveira AP, Mansilla-Soto J, Vogt B, Büning H, Linden RM, Ackermann M, Fraefel C. Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication. PLoS One. 2017 Jan.12(1):e0170908. Pubmedid: 28125695. Pmcid: PMC5268427.
- Mansilla-Soto J, Riviere I, Boulad F, Sadelain M. Cell and Gene Therapy for the Beta-Thalassemias: Advances and Prospects. Hum Gene Ther. 2016 Apr.27(4):295-304. Pubmedid: 27021486. Pmcid: PMC4994056.
- Perna F, Vu LP, Themeli M, Kriks S, Hoya-Arias R, Khanin R, Hricik T, Mansilla-Soto J, Papapetrou EP, Levine RL, Studer L, Sadelain M, Nimer SD. The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells. Stem Cell Reports. 2015 Apr.4(4):658-669. Pubmedid: 25754204. Pmcid: PMC4400644.
- Zarate-Perez F, Mansilla-Soto J, Bardelli M, Burgner JW, Villamil-Jarauta M, Kekilli D, Samso M, Linden RM, Escalante CR. Oligomeric properties of adeno-associated virus Rep68 reflect its multifunctionality. J Virol. 2013 Jan.87(2):1232-1241. Pubmedid: 23152528. Pmcid: PMC3554083.
- Zarate-Perez F, Bardelli M, Burgner JW, Villamil-Jarauta M, Das K, Kekilli D, Mansilla-Soto J, Linden RM, Escalante CR. The interdomain linker of AAV-2 Rep68 is an integral part of its oligomerization domain: role of a conserved SF3 helicase residue in oligomerization. PLoS Pathog. 2012 Nov.8(6):e1002764. Pubmedid: 22719256. Pmcid: PMC3375335.
- Mansilla-Soto J, Rivière I, Sadelain M. Genetic strategies for the treatment of sickle cell anaemia. Brit J Haematol. 2011 Sep.154(6):715-727. Pubmedid: 21707580.
- Mansilla-Soto J, Yoon-Robarts M, Rice WJ, Arya S, Escalante CR, Linden RM. DNA structure modulates the oligomerization properties of the AAV initiator protein Rep68. PLoS Pathog. 2009 Jul.5(7):e1000513. Pubmedid: 19593381. Pmcid: PMC2702170.
- Sawchuk DJ, Mansilla-Soto J, Alarcon C, Singha NC, Langen H, Bianchi ME, Lees-Miller SP, Nussenzweig MC, Cortes P. Ku70/Ku80 and DNA-dependent protein kinase catalytic subunit modulate RAG-mediated cleavage: implications for the enforcement of the 12/23 rule. J Biol Chem. 2004 Jul.279(28):29821-29831. Pubmedid: 15123719.
- Mansilla-Soto J, Cortes P. VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med. 2003 Mar.197(5):543-547. Pubmedid: 12615895. Pmcid: PMC2193822.
- Mc Donnell S, Chaudhry V, Mansilla-Soto J, Zeng ZS, Shu WP, Guillem JG. Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo. Clin Exp Metastas. 1999 Jun.17(4):341-349. Pubmedid: 10545021.
- Besmer E, Mansilla-Soto J, Cassard S, Sawchuk DJ, Brown G, Sadofsky M, Lewis SM, Nussenzweig MC, Cortes P. Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. Mol Cell. 1998 Dec.2(6):817-828. Pubmedid: 9885569.