Featured Publications

Monje, M., Mahdi, J., Majzner, R., Yeom, K. W., Schultz, L. M., Richards, R. M., ... & Mackall, C.L. (2024). Intravenous and intracranial GD2-CAR T cells for H3K27M+ diffuse midline gliomas. Nature, 1-8.

Guerrero, J. A., Klysz, D. D., Chen, Y., Malipatlolla, M., Lone, J., Fowler, C., ... & Mackall, C. L. (2024). GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency. Nature Communications, 15(1), 8658.

Frank, M. J.*, Baird, J. H.*, Kramer, A. M.*, Srinagesh, H. K., Patel, S., Brown, A. K., ... Mackall, C.L., ... & Tunuguntla, R. (2024). CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. The Lancet, 404(10450), 353-363.

Mackall, C. L., Bollard, C. M., Goodman, N., Carr, C., Gardner, R., Rouce, R., ... & Kohn, D. B. (2024). Enhancing pediatric access to cell and gene therapies. Nature Medicine, 1-11.

Yamada-Hunter, S. A.*, Theruvath, J.*, McIntosh, B. J., Freitas, K. A., Lin, F., Radosevich, M. T., Leruste, A., ... & Mackall, C. L. (2024). Engineered CD47 protects T cells for enhanced antitumor immunity. Nature, 1-9.

Doan, A. E.*, Mueller, K. P.*, Chen, A. Y.*, Rouin, G. T., Chen, Y., Daniel, B., ... & Mackall, C.L., Weber, E. W. (2024). FOXO1 is a master regulator of memory programming in CAR T cells. Nature, 1-8.

Tieu, V., Sotillo, E., Bjelajac, J.R., Chen, C., Malipatlolla, M., Guerrero, J.A., ... & Mackall, C.L., Qi, L.S. (2024). A versatile CRISPR-Cas13d platform for multiplexed transcriptomic regulation and metabolic engineering in primary human T cells. Cell.

Klysz, D.D., Fowler, C., Malipatlolla, M., Stuani, L., Freitas, K.A., Chen, Y., ... & Mackall, C.L. (2023). Inosine Induces Stemness Features in CAR T cells and Enhances Potency. Cancer Cell.

Kaczanowska, S.*, Murty, T.*, Alimadadi, A.*, Contreras, C. F., Duault, C., Subrahmanyam, P. B., ... & Mackall, C.L., Ramakrishna, S., Kaplan, R. N. (2023). Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy. Cancer Cell, 42(1), P35-51.E8.

Balke-Want, H., Keerthi, V., Gkitsas, N., Mancini, A. G., Kurgan, G. L., Fowler, C., ... & Mackall, C.L., Feldman, S. A. (2023). Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing. Molecular Cancer, 22(1), 1-16.

Labanieh, L., Mackall, C.L. (2023) CAR immune cells: design principles, resistance and the next generation. Nature, 614, 635–648.

Freitas, K. A.*, Belk, J. A.*, Sotillo, E., Quinn, P. J., Ramello, M. C., Malipatlolla, M., ... & Mackall, C. L. (2022). Enhanced T cell effector activity by targeting the Mediator kinase module. Science, 378(6620).

Good, Z., Spiegel, J.Y., Sahaf, B., Malipatlolla, M., Ehlinger, Z., Kurra, S.... & Mackall, C. L. (2022). Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy. Nature Medicine, 28(9), 1860-1871.

Labanieh, L., Majzner, R. G., Klysz, D., Sotillo, E., Fisher, C. J., Vilches-Moure, J. G., ... & Mackall, C. L. (2022). Enhanced safety and efficacy of protease-regulated CAR-T cell receptors. Cell, 185(10), 1745-1763.

Majzner, R. G., Ramakrishna, S., Yeom, K. W., Patel, S., Chinnasamy, H., Schultz, L. M., Richards, R. M., Jiang, L., Barsan, V., Mancusi, R., Geraghty, A. C., Good, Z., Mochizuki, A. Y., Gillespie, S. M., Toland, A., Mahdi, J., Reschke, A., Nie, E., Chau, I. J., Rotiroti, M. C., … & Monje, M. (2022). GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature, 603(7903), 934-941.

Theruvath, J., Menard, M., Smith, B., Linde, M. H., Coles, G. L., Dalton, G. N., Wu, W., Kiru, L., Delaidelli, A., Sotillo, E., Silberstein, J. L., Geraghty, A. C., Banuelos, A., Radosevich, M. T., Dhingra, S., Heitzeneder, S., Tousley, A., Lattin, J., Xu, P., Huang, J., … & Majzner, R. G. (2022). Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nature Medicine, 28(2), 333-344.

Heitzeneder, S., Bosse, K. R., Zhu, Z., Zhelev, D., Majzner, R. G., Radosevich, M. T., Dhingra, S., Sotillo, E., Buongervino, S., Pascual-Pasto, G., Garrigan, E., Xu, P., Huang, J., Salzer, B., Delaidelli, A., Raman, S., Cui, H., Martinez, B., Bornheimer, S. J., Sahaf, B., … & Mackall, C. L. (2021). GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity. Cancer Cell, S1535-6108(21)00658-9.

Richards, R. M., Zhao, F., Freitas, K. A., Parker, K. R., Xu, P., Fan, A., Sotillo, E., Daugaard, M., Oo, H. Z., Liu, J., Hong, W.-J., Sorensen, P. H., Chang, H. Y., Satpathy, A. T., Majzner, R. G., Majeti, R., & Mackall, C. L. (2021). Not-gated CD93 CAR T cells effectively target AML with minimized endothelial cross-reactivity. Blood Cancer Discovery, 2(6), 648.

Gennert, D. G., Lynn, R. C., Granja, J. M., Weber, E. W., Mumbach, M. R., Zhao, Y., Duren, Z., Sotillo, E., Greenleaf, W. J., Wong, W. H., Satpathy, A. T., Mackall, C. L., & Chang, H. Y. (2021). Dynamic chromatin regulatory landscape of human CAR T cell exhaustion. Proceedings of the National Academy of Sciences of the United States of America, 118(30), e2104758118.

Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Daniel, B., Klysz, D., Malipatlolla, M., Xu, P., Bashti, M., Heitzeneder, S., Labanieh, L., Vandris, P., Majzner, R. G., Qi, Y., Sandor, K., Chen, L. C., … & Mackall, C. L. (2021). Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science, 372(6537), eaba1786.

Theruvath, J., Sotillo, E., Mount, C. W., Graef, C. M., Delaidelli, A., Heitzeneder, S., Labanieh, L., Dhingra, S., Leruste, A., Majzner, R. G., Xu, P., Mueller, S., Yecies, D. W., Finetti, M. A., Williamson, D., Johann, P. D., Kool, M., Pfister, S., Hasselblatt, M., Frühwald, M. C., … & Mackall, C. L. (2020). Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Nature Medicine, 26(5), 712–719.

Weber, E. W., Maus, M. V., & Mackall, C. L. (2020). The Emerging Landscape of Immune Cell Therapies. Cell, 181(1), 46–62. 

Majzner, R. G., Rietberg, S. P., Sotillo, E., Dong, R., Vachharajani, V. T., Labanieh, ... & Mackall, C. L. (2020). Tuning the Antigen Density Requirement for CAR T-cell Activity. Cancer Discovery, 10(5), 702–723.

Murty, S.*, Labanieh, L.*, Murty, T., Gowrishankar, G., Haywood, T., Alam, I. S., ... & Mackall, C. L., Gambhir, S. S. (2020). PET reporter gene imaging and ganciclovir-mediated ablation of chimeric antigen receptor T cells in solid tumors. Cancer Research, 80(21), 4731-4740.

Lynn, R. C., Weber, E. W., Sotillo, E., Gennert, D., Xu, P., Good, Z., Anbunathan, H., Lattin, J., Jones, R., Tieu, V., Nagaraja, S., Granja, J., de Bourcy, C., Majzner, R., Satpathy, A. T., Quake, S. R., Monje, M., Chang, H. Y., & Mackall, C. L. (2019). c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature, 576(7786), 293–300.

Majzner, R. G., & Mackall, C. L. (2019). Clinical lessons learned from the first leg of the CAR T cell journey. Nature Medicine, 25(9), 1341–1355.

Majzner, R. G., Theruvath, J. L., Nellan, A., Heitzeneder, S., Cui, Y., Mount, C. W., Rietberg, S. P., Linde, M. H., Xu, P., Rota, C., Sotillo, E., Labanieh, L., Lee, D. W., Orentas, R. J., Dimitrov, D. S., Zhu, Z., Croix, B. S., Delaidelli, A., Sekunova, A., Bonvini, E., … & Mackall, C. L. (2019). CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Clinical Cancer Research, 25(8), 2560–2574.

Labanieh, L., Majzner, R. G., & Mackall, C. L. (2018). Programming CAR-T cells to kill cancer. Nature Biomedical Engineering, 2(6), 377–391.

Long, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., Kaplan, R. N., Patterson, G. H., Fry, T. J., Orentas, R. J., & Mackall, C. L. (2015). 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nature Medicine, 21(6), 581–590.

All Publications

Crystal Mackall

Publications

  • Clinical and Cytokine Features of Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome. Blood cancer discovery Srinagesh, H. K., Kramer, A. M., Baird, J. H., Reschke, A., Sahaf, B., Cancilla, J., Syal, S., Su, Y. J., Agarwal, N., Jensen, A. M., Schultz, L. M., Jeyakumar, N., Ramakrishna, S., Davis, K. L., Dahiya, S., Feldman, S. A., Mackall, C. L., Muffly, L., Miklos, D. B., Frank, M. J. 2025

    Abstract

    CAR-T cells targeting CD22 (CAR22) are associated with IEC-HS. However, CAR22-related IEC-HS has not been detailed in LBCL or adults with B-ALL. Here, we describe the manifestations of IEC-HS in patients with LBCL and B-ALL. IEC-HS was common, occurring in 19 out of 54 patients (35%); 8 patients required treatment and 11 patients did not. Development of IEC-HS was associated with a higher non-relapse mortality risk yet lower relapse. CAR expansion in peripheral blood significantly associated with IEC-HS severity. Cytokine profiling identified 41 cytokines primarily related to the IFNg, TNFa and IL1 families that correlated strongly with IEC-HS severity. We developed a parsimonious model composed of IFNg, IL10 and IL1RA that accurately predicted grade 2+ IEC-HS on D+14 better than the full signature (AUC 0.93 vs 0.75, p = 0.038). In summary, we found IEC-HS predicts higher NRM and lower relapse after CAR22 and that cytokine signatures predict severe IEC-HS.

    View details for DOI 10.1158/2643-3230.BCD-25-0262

    View details for PubMedID 41411617

  • Enabling access to genetically modified cell therapies through flexible approaches to manufacturing and cost recovery. Journal for immunotherapy of cancer Stewart, M. D., Cabanski, C. R., Allen, J. D., Connolly, J. E., Beneski, B. M., Dropulić, B., Feldman, S. A., Fleisher, L. A., Hanley, P. J., Hege, K., Kekre, N., Fernandez Lynch, H., Mackall, C. L. 2025; 13 (12)

    Abstract

    Genetically modified cell-based therapies hold transformative potential, particularly for patients with rare cancers and ultra-rare diseases. However, progress toward regulatory approval, reimbursement, and broad patient access is often constrained by misaligned regulatory, manufacturing, and financial frameworks that do not reflect the realities of treating small populations and low-throughput production models. Drawing on a collaborative white paper and public meeting convened by Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy in May 2025, this commentary outlines three strategies to streamline regulatory pathways and enable timely, sustainable access: (1) flexible approaches to Chemistry, Manufacturing, and Controls requirements in small populations, (2) adaptable regulatory frameworks to support diverse manufacturing models, and (3) limited cost recovery mechanisms to bridge early access and development gaps. Recent regulatory and policy discussions have echoed these priorities, signaling an opportunity to align oversight with operational realities to advance innovation and access for patients in high-need settings.

    View details for DOI 10.1136/jitc-2025-013518

    View details for PubMedID 41330611

  • Long-term Follow-up of Gastrointestinal CAR T-cell Lymphoma: Homing, Clonal Expansion, and Response to Cyclosporine. Blood Hosoya, H., Bastidas Torres, A. N., Fernandez-Pol, S., Gubatan, J. M., Najidh, S., Duran, G. E., Dong, F., Ehlinger, Z., Lohman, C., Wright, C., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S., Kurtz, D. M., Khodadoust, M. S., Mikkilineni, L. 2025

    Abstract

    CAR T-cell therapy has emerged as a transformative treatment for hematological malignancies, yet its potential to drive lymphomagenesis poses significant clinical concerns. In this study, we investigated the mechanisms underlying CAR T-cell-associated lymphomagenesis in the gastrointestinal (GI) tract on a single case, focusing specifically on the role of integrin a4b7 expression and a predisposing somatic SH2B3 mutation. We observed oligoclonal CAR T-cells homing to and clonally expanding in the GI tract, with the dominant expanded clone harboring both a pathogenic SH2B3 mutation and a CAR transgene integration within a TFCP2 locus. The clonal CAR T-cells subsequently transitioned beyond the GI tract into the peripheral blood, suggesting a potential pathway for systemic dissemination. We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, pre-existing genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR-T lymphomagenesis.

    View details for DOI 10.1182/blood.2025031423

    View details for PubMedID 41288531

  • Transcriptomic Diversity of Pediatric Acute Myeloid Leukemia Genetic Drivers Correlates With Clinical Outcome and Expression of Stemness-Related Genes. Cancer medicine Bubb, Q. R., Sotillo, E., Richards, R. M., Mackall, C. L., Gruber, T. A., Czechowicz, A. 2025; 14 (21): e71325

    Abstract

    Pediatric acute myeloid leukemia (pAML) is comprised of a diverse set of oncogenic drivers (ODs) that have been risk-stratified to inform prognosis and therapeutic decision-making. Despite proteomic, transcriptomic, genetic, and epigenetic characterization of the pAML landscape, questions still remain about why certain ODs have poorer prognoses than others.We analyze a large pAML bulk-RNA dataset (n = 435) and organize ODs along an axis of transcriptomic diversity by calculating the Simpson Diversity Index (SDI) of individual ODs.When comparing patients with low diversity ODs to patients with high diversity ODs, we observe poorer overall survival (HR = 1.877, 95% CI: 1.377-2.558, p = 0.0002) among patients harboring high diversity ODs in addition to an enrichment of stemness-related genes. We observe poorer survival of patients with high diversity ODs even when comparing patients with similar transcriptomic profiles (HR = 3.443, 95% CI: 1.817-6.525, p = 0.0028).We identify a link between transcriptomic diversity, expression of stemness-related genes, and clinical outcome. Higher transcriptomic heterogeneity exhibited by high diversity ODs warrants further attention when identifying patients who can benefit from novel or high-intensity therapy.

    View details for DOI 10.1002/cam4.71325

    View details for PubMedID 41178390

    View details for PubMedCentralID PMC12580620

  • EVALUATION OF B7-H3 IMMUNOHISTOCHEMISTRY IN HIGH-GRADE GLIOMAS FOR CHIMERIC ANTIGEN RECEPTOR T-CELL PREDICTIVE TESTING Dyson, K., Zuraski, C., Solomon, D., Li, G., Stocksdale, B., Song, K., Mahdi, J., Tanner, K., Bertrand, S., Iv, M., Threlkeld, Z., Ramakrishna, S., Sahaf, B., Egeler, E., Tunuguntla, R., Therkelsen, K., Nagpal, S., Lim, M., Monje, M., Scott, B., Mackall, C., Charu, V., Thomas, R. OXFORD UNIV PRESS INC. 2025: v49-v50

    View details for DOI 10.1093/neuonc/noaf201.0195

    View details for Web of Science ID 001613247800006