{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:53:49Z","timestamp":1788850429999,"version":"build-2803163510"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bull Math Biol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>CAR T-cell therapies have demonstrated significant success in treating B-cell leukemia in children and young adults. However, their effectiveness in treating B-cell lymphomas has been limited in comparison to leukemia. In this paper we present a mathematical model that elucidates the dynamics of diffuse large B-cell lymphoma and CAR T-cells in a lymph node. The mathematical model aids in understanding the complex interplay between the cell populations involved and proposes ways to identify potential underlying dynamical causes of treatment failure. We also study the phenomenon of immunosuppression induced by tumor cells and theoretically demonstrate its impact on cell dynamics. Through the examination of various response scenarios, we underscore the significance of product characteristics in treatment outcomes.<\/jats:p>","DOI":"10.1007\/s11538-025-01417-1","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T11:33:01Z","timestamp":1738927981000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node"],"prefix":"10.1007","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-1502","authenticated-orcid":false,"given":"Soukaina","family":"Sabir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odelaisy","family":"Le\u00f3n-Triana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Barrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M.","family":"P\u00e9rez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"1417_CR1","doi-asserted-by":"publisher","first-page":"5171","DOI":"10.3390\/cancers13205171","volume":"13","author":"V Adhikarla","year":"2021","unstructured":"Adhikarla V, Awuah D, Brummer AB, Caserta E, Krishnan A, Pichiorri F, Minnix M, Shively JE, Wong JYC, Wang X, Rockne RC (2021) A mathematical modeling approach for targeted radionuclide and chimeric antigen receptor T cell combination therapy. Cancers 13:5171. https:\/\/doi.org\/10.3390\/cancers13205171","journal-title":"Cancers"},{"key":"1417_CR2","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/s41586-023-06243-w","volume":"619","author":"DJ Baker","year":"2023","unstructured":"Baker DJ, Arany Z, Baur JA, Epstein JA, June CH (2023) CAR T therapy beyond cancer: the evolution of a living drug. Nature 619:707\u2013715. https:\/\/doi.org\/10.1038\/s41586-023-06243-w","journal-title":"Nature"},{"issue":"12","key":"1417_CR3","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.3390\/cancers13122941","volume":"13","author":"LRC Barros","year":"2021","unstructured":"Barros LRC, Paix\u00e3o EA, Valli AMP, Naozuka GT, Fassoni AC, Almeida RC (2021) CARTmath\u2014a mathematical model of CAR-T immunotherapy in preclinical studies of hematological cancers. Cancers 13(12):2941. https:\/\/doi.org\/10.3390\/cancers13122941","journal-title":"Cancers"},{"issue":"3","key":"1417_CR4","doi-asserted-by":"publisher","first-page":"379","DOI":"10.34768\/AMCS-2023-0027","volume":"33","author":"M Bodnar","year":"2023","unstructured":"Bodnar M, Fory\u015b U, Piotrowska MJ, Bodzioch M, Romero-Rosales JA, Belmonte-Beitia J (2023) On the analysis of a mathematical model of CAR T-cell therapy for glioblastoma: insights from a mathematical model. Int J Appl Math Comput Sci 33(3):379\u2013394. https:\/\/doi.org\/10.34768\/AMCS-2023-0027","journal-title":"Int J Appl Math Comput Sci"},{"key":"1417_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009504","volume":"18","author":"AB Brummer","year":"2022","unstructured":"Brummer AB, Yang X, Ma E, Gutova M, Brown CE, Rockne RC (2022) Dose-dependent thresholds of dexamethasone destabilize CAR T-cell treatment efficacy. PLoS Comput Biol 18:e1009504. https:\/\/doi.org\/10.1371\/journal.pcbi.1009504","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"1417_CR6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41571-023-00754-1","volume":"20","author":"KM Cappell","year":"2023","unstructured":"Cappell KM, Kochenderfer JN (2023) Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol 20(6):359\u2013371","journal-title":"Nat Rev Clin Oncol"},{"issue":"22","key":"1417_CR7","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.3390\/cells11223626","volume":"11","author":"A Cheever","year":"2022","unstructured":"Cheever A, Townsend M, O\u2019Neill K (2022) Tumor microenvironment immunosuppression: a roadblock to CAR T-cell advancement in solid tumors. Cells 11(22):3626. https:\/\/doi.org\/10.3390\/cells11223626","journal-title":"Cells"},{"issue":"12","key":"1417_CR8","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2015.1053684","volume":"4","author":"AJ Davenport","year":"2015","unstructured":"Davenport AJ, Jenkins MR, Ritchie DS, Prince HM, Trapani JA, Kershaw MH, Darcy PK, Neeson PJ (2015) CAR T-cells are serial killers. OncoImmunology 4(12):e1053684. https:\/\/doi.org\/10.1080\/2162402x.2015.1053684","journal-title":"OncoImmunology"},{"key":"1417_CR9","unstructured":"Doedel E (1981) AUTO: a program for the automatic bifurcation analysis of autonomous systems. In: Proceedings of the tenth Manitoba conference on numerical mathematics and computing, vol I (Winnipeg, Man., 1980), vol 30, pp 265\u2013284"},{"key":"1417_CR10","unstructured":"Doedel EJ, Paffenroth RC, Champneys AR, Fairgrieve TF, Kuznetsov YA, Oldeman BE, Sandstede B, Wang XJ. Auto2000. http:\/\/cmvl.cs.concordia.ca\/auto"},{"issue":"5","key":"1417_CR11","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1200\/JCO.19.01892","volume":"38","author":"NV Frey","year":"2020","unstructured":"Frey NV, Shaw PA, Hexner EO et al (2020) Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia. JCO 38(5):415\u2013422. https:\/\/doi.org\/10.1200\/JCO.19.01892","journal-title":"JCO"},{"issue":"43","key":"1417_CR12","first-page":"2714","volume":"173","author":"UC Fr\u00f8lund","year":"2011","unstructured":"Fr\u00f8lund UC, Nielsen SL, Hansen PB (2011) Burkitt lymphoma is a highly malign tumour with a doubling time of twenty-four hours. Ugeskr Laeger 173(43):2714\u20132718","journal-title":"Ugeskr Laeger"},{"issue":"12","key":"1417_CR13","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.3390\/bioengineering10121360","volume":"10","author":"SR Ganesh","year":"2023","unstructured":"Ganesh SR, Roth CM, Parekkadan B (2023) Simulating interclonal interactions in diffuse large B-cell lymphoma. Bioengineering 10(12):1360. https:\/\/doi.org\/10.3390\/bioengineering10121360","journal-title":"Bioengineering"},{"key":"1417_CR14","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1038\/s41591-019-0549-5","volume":"25","author":"S Ghorashian","year":"2019","unstructured":"Ghorashian S, Kramer AM, Onuoha S et al (2019) Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med 25:1408\u20131414. https:\/\/doi.org\/10.1038\/s41591-019-0549-5","journal-title":"Nat Med"},{"key":"1417_CR15","doi-asserted-by":"publisher","unstructured":"Guckenheimer J, Holmes P (1983) Nonlinear oscillations, dynamical systems, and bifurcations of vector fields. Springer, New York. https:\/\/doi.org\/10.1007\/978-1-4612-1140-2","DOI":"10.1007\/978-1-4612-1140-2"},{"key":"1417_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103941","volume":"77","author":"D Gumber","year":"2022","unstructured":"Gumber D, Wang LD (2022) Improving CAR-T immunotherapy: overcoming the challenges of T cell exhaustion. EBioMedicine 77:103941. https:\/\/doi.org\/10.1016\/j.ebiom.2022.103941","journal-title":"EBioMedicine"},{"key":"1417_CR17","doi-asserted-by":"publisher","unstructured":"Kimmel GJ, Locke FL, Altrock PM (2021) The roles of T cell competition and stochastic extinction events in chimeric antigen receptor T cell therapy. Proc R Soc B. https:\/\/doi.org\/10.1098\/rspb.2021.0229","DOI":"10.1098\/rspb.2021.0229"},{"key":"1417_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03442-3","author":"T Kouro","year":"2022","unstructured":"Kouro T, Himuro H, Sasada T (2022) Exhaustion of CAR T cells: potential causes and solutions. J Transl Med. https:\/\/doi.org\/10.1186\/s12967-022-03442-3","journal-title":"J Transl Med"},{"issue":"2","key":"1417_CR19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/s0092-8240(05)80260-5","volume":"56","author":"V Kuznetsov","year":"1994","unstructured":"Kuznetsov V, Makalkin I, Taylor M, Perelson A (1994) Nonlinear dynamics of immunogenic tumors: parameter estimation and global bifurcation analysis. Bull Math Biol 56(2):295\u2013321. https:\/\/doi.org\/10.1016\/s0092-8240(05)80260-5","journal-title":"Bull Math Biol"},{"issue":"3","key":"1417_CR20","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/bf00430662","volume":"389","author":"W Lang","year":"1980","unstructured":"Lang W, Kienzle S, Diehl V (1980) Proliferation kinetics of malignant non-Hodgkin\u2019s lymphomas related to histopathology of lymph node biopsies. Virchows Arch A Path Anat Histol 389(3):397\u2013407. https:\/\/doi.org\/10.1007\/bf00430662","journal-title":"Virchows Arch A Path Anat Histol"},{"key":"1417_CR21","doi-asserted-by":"publisher","unstructured":"Le\u00f3n-Triana O, P\u00e9rez-Mart\u00ednez A, Ram\u00edrez-Orellana M, P\u00e9rez-Garc\u00eda VM (2021a) Dual-target CAR-Ts with on- and off-tumour activity may override immune suppression in solid cancers: a mathematical proof of concept. Cancers 13(4):703. https:\/\/doi.org\/10.3390\/cancers13040703","DOI":"10.3390\/cancers13040703"},{"key":"1417_CR22","doi-asserted-by":"publisher","unstructured":"Le\u00f3n-Triana O, Sabir S, Calvo GF, Belmonte-Beitia J, Chuli\u00e1n S, Mart\u00ednez-Rubio \u00c1, Rosa M, P\u00e9rez-Mart\u00ednez A, Ramirez-Orellana M, P\u00e9rez-Garc\u00eda VM (2021b) CAR T cell therapy in B-cell acute lymphoblastic leukaemia: insights from mathematical models. Commun Nonlinear Sci Numer Simul 94:105570. https:\/\/doi.org\/10.1016\/j.cnsns.2020.105570","DOI":"10.1016\/j.cnsns.2020.105570"},{"key":"1417_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuno.2023.100022","volume":"9","author":"R Li","year":"2023","unstructured":"Li R, Sahoo P, Wang D, Wang Q, Brown CE, Rockne RC et al (2023) Modeling interaction of Glioma cells and CAR T-cells considering multiple CAR T-cells bindings. ImmunoInformatics 9:100022. https:\/\/doi.org\/10.1016\/j.immuno.2023.100022","journal-title":"ImmunoInformatics"},{"issue":"12","key":"1417_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005360","volume":"10","author":"L Liu","year":"2022","unstructured":"Liu L, Ma C, Zhang Z, Witkowski MT, Aifantis I, Ghassemi S, Chen W (2022) Computational model of CAR T-cell immunotherapy dissects and predicts leukemia patient responses at remission, resistance, and relapse. J Immunother Cancer 10(12):e005360. https:\/\/doi.org\/10.1136\/jitc-2022-005360","journal-title":"J Immunother Cancer"},{"issue":"5","key":"1417_CR25","doi-asserted-by":"publisher","first-page":"4429","DOI":"10.3934\/mbe.2022205","volume":"19","author":"KJ Mahasa","year":"2022","unstructured":"Mahasa KJ, Ouifki R, Eladdadi A, de Pillis L (2022) A combination therapy of oncolytic viruses and chimeric antigen receptor T cells: a mathematical model proof-of-concept. Math Biosic Eng 19(5):4429\u201357. https:\/\/doi.org\/10.3934\/mbe.2022205","journal-title":"Math Biosic Eng"},{"issue":"12","key":"1417_CR26","doi-asserted-by":"publisher","first-page":"6371","DOI":"10.3390\/ijms22126371","volume":"22","author":"\u00c1 Mart\u00ednez-Rubio","year":"2021","unstructured":"Mart\u00ednez-Rubio \u00c1, Chuli\u00e1n S, Bl\u00e1zquez Go\u00f1i C, Ram\u00edrez Orellana M, P\u00e9rez Mart\u00ednez A, Navarro-Zapata A, Ferreras C, P\u00e9rez-Garc\u00eda VM, Rosa M (2021) A mathematical description of the bone marrow dynamics during CAR T-cell therapy in B-cell childhood acute lymphoblastic leukemia. Int J Mol Sci 22(12):6371. https:\/\/doi.org\/10.3390\/ijms22126371","journal-title":"Int J Mol Sci"},{"issue":"4","key":"1417_CR27","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2014.1002720","volume":"4","author":"S Nayar","year":"2015","unstructured":"Nayar S, Dasgupta P, Galustian C (2015) Extending the lifespan and efficacies of immune cells used in adoptive transfer for cancer immunotherapies\u2014a review. OncoImmunology 4(4):e1002720. https:\/\/doi.org\/10.1080\/2162402x.2014.1002720","journal-title":"OncoImmunology"},{"issue":"1","key":"1417_CR28","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41540-023-00298-1","volume":"9","author":"B Oca\u00f1a-Tienda","year":"2023","unstructured":"Oca\u00f1a-Tienda B, P\u00e9rez-Beteta J, Jim\u00e9nez-S\u00e1nchez J, Molina-Garc\u00eda D, Ortiz de Mendivil A, Asenjo B, Albillo D, P\u00e9rez-Romasanta LA, Valiente M, Zhu L, Garc\u00eda-G\u00f3mez P, Gonz\u00e1lez-Del Portillo E, Llorente M, Carballo N, Arana E, P\u00e9rez-Garc\u00eda VM (2023) Growth exponents reflect evolutionary processes and treatment response in brain metastases. npj Syst Biol Appl 9(1):35. https:\/\/doi.org\/10.1038\/s41540-023-00298-1","journal-title":"npj Syst Biol Appl"},{"issue":"5","key":"1417_CR29","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s11538-021-00869-5","volume":"83","author":"K Owens","year":"2021","unstructured":"Owens K, Bozic I (2021) Modeling CAR T-cell therapy with patient preconditioning. Bull Math Biol 83(5):42. https:\/\/doi.org\/10.1007\/s11538-021-00869-5","journal-title":"Bull Math Biol"},{"issue":"12","key":"1417_CR30","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1038\/s41567-020-0978-6","volume":"16","author":"VM P\u00e9rez-Garc\u00eda","year":"2020","unstructured":"P\u00e9rez-Garc\u00eda VM, Calvo GF, Bosque JJ, Le\u00f3n-Triana O, Jim\u00e9nez J, P\u00e9rez-Beteta J, Belmonte-Beitia J, Valiente M, Zhu L, Garc\u00eda-G\u00f3mez P, S\u00e1nchez-G\u00f3mez P, Hern\u00e1ndez-San Miguel E, Hortig\u00fcela R, Azimzade Y, Molina-Garc\u00eda D, Mart\u00ednez \u00c1, Acosta Rojas \u00c1, Ortiz de Mendivil A, Vallette F, Schucht P, Murek M, P\u00e9rez-Cano M, Albillo D, Honguero Mart\u00ednez AF, Jim\u00e9nez Londo\u00f1o GA, Arana E, Garc\u00eda Vicente AM (2020) Universal scaling laws rule explosive growth in human cancers. Nat Phys 16(12):1232\u20137. https:\/\/doi.org\/10.1038\/s41567-020-0978-6","journal-title":"Nat Phys"},{"key":"1417_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnsns.2020.105684","volume":"96","author":"VM P\u00e9rez-Garc\u00eda","year":"2021","unstructured":"P\u00e9rez-Garc\u00eda VM, Le\u00f3n-Triana O, Rosa M, P\u00e9rez-Mart\u00ednez A (2021) CAR T cells for T-cell leukemias: insights from mathematical models. Commun Nonlinear Sci Numer Simul 96:105684. https:\/\/doi.org\/10.1016\/j.cnsns.2020.105684","journal-title":"Commun Nonlinear Sci Numer Simul"},{"issue":"2","key":"1417_CR32","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s11538-013-9925-3","volume":"76","author":"K Roesch","year":"2013","unstructured":"Roesch K, Hasenclever D, Scholz M (2013) Modelling lymphoma therapy and outcome. Bull Math Biol 76(2):401\u201330. https:\/\/doi.org\/10.1007\/s11538-013-9925-3","journal-title":"Bull Math Biol"},{"issue":"162","key":"1417_CR33","doi-asserted-by":"publisher","first-page":"20190734","DOI":"10.1098\/rsif.2019.0734","volume":"17","author":"P Sahoo","year":"2020","unstructured":"Sahoo P, Yang X, Abler D, Maestrini D, Adhikarla V, Frankhouser D, Cho H, Machuca V, Wang D, Barish M, Gutova M, Branciamore S, Brown CE, Rockne RC (2020) Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data. J R Soc Interface 17(162):20190734. https:\/\/doi.org\/10.1098\/rsif.2019.0734","journal-title":"J R Soc Interface"},{"issue":"2","key":"1417_CR34","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.cpc.2009.09.018","volume":"181","author":"A Saltelli","year":"2010","unstructured":"Saltelli A, Annoni P, Azzini I, Campolongo F, Ratto M, Tarantola S (2010) Variance based sensitivity analysis of model output. Design and estimator for the total sensitivity index. Comput Phys Commun 181(2):259\u201370. https:\/\/doi.org\/10.1016\/j.cpc.2009.09.018","journal-title":"Comput Phys Commun"},{"key":"1417_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.apm.2023.08.029","volume":"125","author":"DS Santurio","year":"2024","unstructured":"Santurio DS, Paix\u00e3o EA, Barros LRC, Almeida RC, Fassoni AC (2024) Mechanisms of resistance to CAR T-cell immunotherapy: insights from a mathematical model. Appl Math Model 125:1\u201315. https:\/\/doi.org\/10.1016\/j.apm.2023.08.029","journal-title":"Appl Math Model"},{"issue":"7","key":"1417_CR36","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1182\/blood.2018883421","volume":"134","author":"CS Sauter","year":"2019","unstructured":"Sauter CS, Senechal B, Rivi\u00e8re I et al (2019) CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood 134(7):626\u2013635. https:\/\/doi.org\/10.1182\/blood.2018883421","journal-title":"Blood"},{"issue":"9","key":"1417_CR37","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1056\/nejmra2027612","volume":"384","author":"LH Sehn","year":"2021","unstructured":"Sehn LH, Salles G (2021) diffuse large B-cell lymphoma. N Engl J Med 384(9):842\u201358. https:\/\/doi.org\/10.1056\/nejmra2027612","journal-title":"N Engl J Med"},{"issue":"8","key":"1417_CR38","doi-asserted-by":"publisher","DOI":"10.1063\/5.0206341","volume":"34","author":"S Serrano","year":"2024","unstructured":"Serrano S, Barrio R, Mart\u00ednez-Rubio A, Belmonte-Beitia J, P\u00e9rez-Garc\u00eda VM (2024) Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model. Chaos Interdiscip J Nonlinear Sci 34(8):083142. https:\/\/doi.org\/10.1063\/5.0206341","journal-title":"Chaos Interdiscip J Nonlinear Sci"},{"issue":"8","key":"1417_CR39","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.3390\/biomedicines10081960","volume":"10","author":"S Sheikh","year":"2022","unstructured":"Sheikh S, Migliorini D, Lang N (2022) CAR T-based therapies in lymphoma: a review of current practice and perspectives. Biomedicines 10(8):1960. https:\/\/doi.org\/10.3390\/biomedicines10081960","journal-title":"Biomedicines"},{"issue":"5","key":"1417_CR40","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/psp4.12388","volume":"8","author":"AM Stein","year":"2019","unstructured":"Stein AM, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, Boyer MW, August KJ, Levine BL, Tomassian L, Shah S, Leung M, Huang P, Awasthi R, Mueller KT, Wood PA, June CH (2019) Tisagenlecleucel model-based cellular kinetic analysis of chimeric antigen receptor-T cells. CPT Pharmacom Syst Pharma 8(5):285\u201395. https:\/\/doi.org\/10.1002\/psp4.12388","journal-title":"CPT Pharmacom Syst Pharma"},{"key":"1417_CR41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","volume":"11","author":"RC Sterner","year":"2021","unstructured":"Sterner RC, Sterner RM (2021) CAR T-cell therapy: current limitations and potential strategies. Blood Cancer J 11:69. https:\/\/doi.org\/10.1038\/s41408-021-00459-7","journal-title":"Blood Cancer J"},{"issue":"1","key":"1417_CR42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3390\/medsci9010005","volume":"9","author":"KC Thandra","year":"2021","unstructured":"Thandra KC, Barsouk A, Saginala K, Padala SA, Barsouk A, Rawla P (2021) Epidemiology of non-Hodgkin\u2019s lymphoma. Med Sci 9(1):5. https:\/\/doi.org\/10.3390\/medsci9010005","journal-title":"Med Sci"},{"issue":"1","key":"1417_CR43","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3109\/02841868909111193","volume":"28","author":"M Tubiana","year":"1989","unstructured":"Tubiana M (1989) Tumor cell proliferation kinetics and tumor growth rate. Acta Oncol 28(1):113\u201321. https:\/\/doi.org\/10.3109\/02841868909111193","journal-title":"Acta Oncol"},{"key":"1417_CR44","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.273.5271.104","volume":"273","author":"A Viola","year":"1996","unstructured":"Viola A, Lanzavecchia A (1996) T cell activation determined by T cell receptor number and tunable thresholds. Science 273:104\u2013106. https:\/\/doi.org\/10.1126\/science.273.5271.104","journal-title":"Science"},{"issue":"5","key":"1417_CR45","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1053\/j.seminhematol.2023.11.004","volume":"60","author":"SS Wang","year":"2023","unstructured":"Wang SS (2023) Epidemiology and etiology of diffuse large B-cell lymphoma. Semin Hematol 60(5):255\u2013266. https:\/\/doi.org\/10.1053\/j.seminhematol.2023.11.004","journal-title":"Semin Hematol"},{"issue":"12","key":"1417_CR46","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.trecan.2022.07.007","volume":"8","author":"B Weigelin","year":"2022","unstructured":"Weigelin B, Friedl P (2022) T cell-mediated additive cytotoxicity death by multiple bullets. Trends Cancer 8(12):980\u2013987. https:\/\/doi.org\/10.1016\/j.trecan.2022.07.007","journal-title":"Trends Cancer"},{"issue":"1","key":"1417_CR47","doi-asserted-by":"publisher","first-page":"5217","DOI":"10.1038\/s41467-021-25282-3","volume":"12","author":"B Weigelin","year":"2021","unstructured":"Weigelin B, den Boer AT, Wagena E, Broen K, Dolstra H, de Boer RJ, Figdor CG, Textor J, Friedl P (2021) Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity. Nat Commun 12(1):5217. https:\/\/doi.org\/10.1038\/s41467-021-25282-3","journal-title":"Nat Commun"},{"key":"1417_CR48","doi-asserted-by":"publisher","unstructured":"Wiggins S (2003) Introduction to applied nonlinear dynamical systems and chaos. Springer, Berlin. https:\/\/doi.org\/10.1007\/b97481","DOI":"10.1007\/b97481"},{"key":"1417_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.927153","volume":"13","author":"X Zhang","year":"2022","unstructured":"Zhang X, Zhu L, Zhang H, Chen S, Xiao Y (2022) CAR T-cell therapy in hematological malignancies: current opportunities and challenges. Front Immunol 13:927153. https:\/\/doi.org\/10.3389\/fimmu.2022.927153","journal-title":"Front Immunol"}],"container-title":["Bulletin of Mathematical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-025-01417-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11538-025-01417-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-025-01417-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T13:45:26Z","timestamp":1740404726000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11538-025-01417-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1417"],"URL":"https:\/\/doi.org\/10.1007\/s11538-025-01417-1","relation":{},"ISSN":["0092-8240","1522-9602"],"issn-type":[{"value":"0092-8240","type":"print"},{"value":"1522-9602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]},"assertion":[{"value":"31 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"40"}}