Tara Murty

All Publications

• Low Occurrence of Ocular Adverse Events after CAR-T Cell Therapy. Ocular oncology and pathology Murty, T., Wai, K. M., Rahimy, E., Mruthyunjaya, P. 2025; 11 (2): 104-108

  Abstract

  Chimeric antigen receptor (CAR)-T cell therapies have demonstrated remarkable therapeutic efficacy in leukemias and lymphomas that were previously considered incurable. However, concerns persist over potential risks related to toxicities, including those secondary to activation of the patient's immune system.To investigate ocular adverse effects (o-AEs) associated with CAR-T cell therapy, a retrospective cohort study was designed in which data were obtained from the TriNetX aggregated electronic health records database through August 2024, with data analysis performed in August 2024. Billing codes were used to identify patients receiving autologous CAR-T therapy approved by the US Food and Drug Administration (FDA) for the treatment of a hematological malignancy: tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, idecabtagene vicleucel, or axicabtagene ciloleucel.In a cohort of 684 patients on CAR-T therapy with at least 6 months of follow-up, the most prevalent o-AEs were related to vision changes (1.9%), which included vitreous opacities, visual disturbances, diplopia, and visual discomfort; inflammation (1.8%), which included optic neuritis, conjunctivitis, optic papillitis, chorioretinal inflammation, iridocyclitis, zoster ocular disease; and dry eyes (1.6%), which included dry eye syndrome, keratitis, and ocular manifestations of Vitamin A deficiency.In the period of 6 months following CAR-T therapy infusion, o-AEs were rare in patients receiving CAR-T cell therapy, indicating that patients without existing eye conditions do not need routine prescreening or directed follow-up after treatment, unless symptomatic. Ongoing monitoring and reporting of ocular adverse events will be important given the durable effects of CAR-T therapy in the treatment of hematologic cancers as well as increasing indications for CAR-T therapy in malignant and nonmalignant disease.

  View details for DOI 10.1159/000543055

  View details for PubMedID 40726603

  View details for PubMedCentralID PMC12296209

• Uveal melanoma following Bruton's tyrosine inhibitor use for the treatment of hematologic malignancies. American journal of ophthalmology case reports Murty, T., Lin, J. H., Mruthyunjaya, P. 2025; 38: 102345

  Abstract

  Purpose: To report two new cases and summarize one case of uveal melanoma following treatment of hematologic malignancies with Bruton's tyrosine kinase inhibitors.Observations: A 71-year-old male, with a history of Waldenstrom macroglobulinemia treated with an anti-CD20 antibody and BTKi, was diagnosed with a choroidal melanoma with intraocular metastasis. A 73-year-old female, with a history of Mantle Cell Lymphoma treated with an alkylating chemotherapy and an anti-CD20 antibody, relapse, and subsequent treatment with BTKi, was diagnosed with a uveal melanoma.Conclusions and Importance: Patients being treated with BTK inhibitors may be at higher risk for the development of uveal melanoma. Based on our findings, we recommend increased surveillance of this patient population for secondary primary or metastatic uveal melanoma. Continued documentation of occurrence in conjunction with research at a molecular and cellular level are warranted to better understand the impact of systemic cancer therapies on secondary malignancies.

  View details for DOI 10.1016/j.ajoc.2025.102345

  View details for PubMedID 40475129

• Low Occurrence of Ocular Adverse Events after CAR-T Cell Therapy OCULAR ONCOLOGY AND PATHOLOGY Murty, T., Wai, K. M., Rahimy, E., Mruthyunjaya, P. 2025

  View details for DOI 10.1159/000543055

  View details for Web of Science ID 001438706600001

• CD22-Directed CAR T Cell Single Cell Multiomic Features Associated with Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) Kramer, A., Murty, T., Chen, Y., Srinagesh, H., Hamilton, M. P., Mo, K. C., Prabhu, S., Desai, M., Kuo, A., Ehlinger, Z., Reynolds, W. D., Baird, J. H., Su, Y., Agarwal, N., Sahaf, B., Muffly, L., Mackall, C. L., Miklos, D. B., Frank, M. J., Good, Z. ELSEVIER. 2024: 911-912

  View details for DOI 10.1182/blood-2024-198688

  View details for Web of Science ID 001412850300005

• PRC2-AgeIndex as a universal biomarker of aging and rejuvenation. Nature communications Moqri, M., Cipriano, A., Simpson, D. J., Rasouli, S., Murty, T., de Jong, T. A., Nachun, D., de Sena Brandine, G., Ying, K., Tarkhov, A., Aberg, K. A., van den Oord, E., Zhou, W., Smith, A., Mackall, C., Gladyshev, V. N., Horvath, S., Snyder, M. P., Sebastiano, V. 2024; 15 (1): 5956

  Abstract

  DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the "PRC2-AgeIndex," defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.

  View details for DOI 10.1038/s41467-024-50098-2

  View details for PubMedID 39009581

  View details for PubMedCentralID PMC11250797

• Engineered CD47 protects T cells for enhanced antitumour immunity. Nature Yamada-Hunter, S. A., Theruvath, J., McIntosh, B. J., Freitas, K. A., Lin, F., Radosevich, M. T., Leruste, A., Dhingra, S., Martinez-Velez, N., Xu, P., Huang, J., Delaidelli, A., Desai, M. H., Good, Z., Polak, R., May, A., Labanieh, L., Bjelajac, J., Murty, T., Ehlinger, Z., Mount, C. W., Chen, Y., Heitzeneder, S., Marjon, K. D., Banuelos, A., Khan, O., Wasserman, S. L., Spiegel, J. Y., Fernandez-Pol, S., Kuo, C. J., Sorensen, P. H., Monje, M., Majzner, R. G., Weissman, I. L., Sahaf, B., Sotillo, E., Cochran, J. R., Mackall, C. L. 2024

  Abstract

  Adoptively transferred T cells and agents designed to block the CD47-SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours.

  View details for DOI 10.1038/s41586-024-07443-8

  View details for PubMedID 38750365

  View details for PubMedCentralID 4182950

• Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy. Cancer cell Kaczanowska, S., Murty, T., Alimadadi, A., Contreras, C. F., Duault, C., Subrahmanyam, P. B., Reynolds, W., Gutierrez, N. A., Baskar, R., Wu, C. J., Michor, F., Altreuter, J., Liu, Y., Jhaveri, A., Duong, V., Anbunathan, H., Ong, C., Zhang, H., Moravec, R., Yu, J., Biswas, R., Van Nostrand, S., Lindsay, J., Pichavant, M., Sotillo, E., Bernstein, D., Carbonell, A., Derdak, J., Klicka-Skeels, J., Segal, J. E., Dombi, E., Harmon, S. A., Turkbey, B., Sahaf, B., Bendall, S., Maecker, H., Highfill, S. L., Stroncek, D., Glod, J., Merchant, M., Hedrick, C. C., Mackall, C. L., Ramakrishna, S., Kaplan, R. N. 2023

  Abstract

  Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3+ monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3- classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.

  View details for DOI 10.1016/j.ccell.2023.11.011

  View details for PubMedID 38134936

• Deep myeloid cell profiling provides new insights into modulators of CAR T cell expansion in patients with pediatric solid tumors Kaczanowska, S., Murty, T., Alimadadi, A., Contreras, C. F., Hedrick, C. C., Ramakrishna, S., Kaplan, R. AMER ASSOC IMMUNOLOGISTS. 2023

  View details for DOI 10.4049/jimmunol.210.Supp.62.09

  View details for Web of Science ID 001106506500098

• Caudolenticular Gray Bridges of the Brain: A Magnetic Resonance Imaging Study. Clinical anatomy (New York, N.Y.) Dang, B., Necker, F. N., Dhawan, S. S., Murty, T., Massoud, T. F. 2023

  Abstract

  The caudolenticular (or transcapsular) gray bridges (CLGBs) connect the caudate nucleus (CN) and putamen across the internal capsule. The CLGBs function as the main efferent terminus from premotor and supplementary motor area cortex to the basal ganglia (BG). We conjectured if inherent variations in numbers and sizes of CLGBs could contribute to abnormal cortical-subcortical connectivity in Parkinson's disease (PD), a neurodegenerative disorder featuring a hindrance of BG processing. However, there are no literature accounts of normative anatomy and morphometry of CLGBs. We therefore retrospectively analyzed axial and coronal 3T FSPGR MRIs of 34 healthy individuals for bilateral CLGBs symmetry, their numbers, dimensions of thickest and longest bridge, and axial surface areas of CN head and putamen. We calculated Evans' index (EI) to account for any brain atrophy. We statistically tested associations between sex or age and measured dependent variables, and linear correlations between all measured variables (significance at p<.05). Study subjects were F:M=23:11 with mean age 49.9 years. All EI's were normal (<.3). All but three CLGBs were bilaterally symmetrical with a mean 7.4 CLGBs per side. Mean CLGBs thickness and lengths were 1.0mm and 4.6mm, respectively; CN head and putamen areas were 205mm2 and 382.0mm2 , respectively. Females had thicker CLGBs (p=.02) but we found no significant interactions between sex or age and measured dependent variables, and no correlations between CN head or putamen areas and CLGBs dimensions. These normative MRI dimensions of the CLGBs will help guide future studies on the possible role of CLGBs morphometry in PD predisposition.

  View details for DOI 10.1002/ca.24026

  View details for PubMedID 36795325

• Portal Venous Aneurysm. Radiology Murty, T., Negrete, L. 2023: 221311

  Abstract

  Supplemental material is available for this article.

  View details for DOI 10.1148/radiol.221311

  View details for PubMedID 36749214

• DEFINING T CELL EXHAUSTION AND MEMORY CORRELATES OF GD2 CAR T CELL EXPANSION IN PEDIATRIC PATIENTS WITH SOLID TUMOR MALIGNANCIES Murty, T., Ramakrishna, S., Kaczanowska, S., Contreras, C., Duault, C., Balasubrahmanyam, P., Reynolds, W., Baskar, R., Jhaveri, A., Liu, Y., Altreuter, J., Michor, F., Pichavant, M., Sahaf, B., Bendall, S., Maecker, H., Merchant, M., Mackall, C., Kaplan, R. BMJ PUBLISHING GROUP. 2022: A381

  View details for DOI 10.1136/jitc-2022-SITC2022.0362

  View details for Web of Science ID 000919423400358

• DEEP MYELOID CELL PROFILING PROVIDES NEW INSIGHTS INTO MODULATORS OF CAR T CELL EXPANSION IN PATIENTS WITH SOLID TUMOR MALIGNANCIES Kaczanowska, S., Ramakrishna, S., Murty, T., Contreras, C., Alimadadi, A., Gutierrez, N., Jhaveri, A., Liu, Y., Altreuter, J., Michor, F., Duault, C., Balasubrahmanyam, P., Reynolds, W., Baskar, R., Pichavant, M., Sahaf, B., Bendall, S., Maecker, H., Merchant, M., Mackall, C., Hedrick, C., Kaplan, R. BMJ PUBLISHING GROUP. 2022: A418

  View details for DOI 10.1136/jitc-2022-SITC2022.0397

  View details for Web of Science ID 000919423400393

• Exploring the role of telomerase in senescence and exhaustion in CAR T cell immunotherapy Murty, T., Ramello, M. C., Sotillo, E., Chen, L., Artandi, S. A., Mackall, C. L. AMER ASSOC CANCER RESEARCH. 2022

  View details for Web of Science ID 000892509507408

• Enhanced safety and efficacy of protease-regulated CAR-T cell receptors. Cell Labanieh, L., Majzner, R. G., Klysz, D., Sotillo, E., Fisher, C. J., Vilches-Moure, J. G., Pacheco, K. Z., Malipatlolla, M., Xu, P., Hui, J. H., Murty, T., Theruvath, J., Mehta, N., Yamada-Hunter, S. A., Weber, E. W., Heitzeneder, S., Parker, K. R., Satpathy, A. T., Chang, H. Y., Lin, M. Z., Cochran, J. R., Mackall, C. L. 2022

  Abstract

  Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted in tumor eradication in the absence of toxicity. SNIP CARs enable remote tuning of CAR activity, which provides solutions to safety and efficacy barriers that are currently limiting progress in using CAR-T cells to treat solid tumors.

  View details for DOI 10.1016/j.cell.2022.03.041

  View details for PubMedID 35483375

• Gene Editing to Enhance the Efficacy of Cancer Cell Therapies. Molecular therapy : the journal of the American Society of Gene Therapy Murty, T., Mackall, C. L. 2021

  Abstract

  Adoptive T cell therapies have shown impressive signals of activity, but their clinical impact could be enhanced by technologies to increase T cell potency and diminish the cost and labor involved in manufacturing these products. Gene editing platforms are under study in this arena to 1) enhance immune cell potency by knocking out molecules that inhibit immune responses; 2) deliver genetic payloads into precise genomic locations and thereby enhance safety and/or improve the gene expression profile by leveraging physiologic promoters, enhancers, and repressors; and 3) enable off-the-shelf therapies by preventing alloreactivity and immune rejection (Figure 1). This review will discuss gene editing approaches that have been most well studied in the context of human T cells and adoptive T cell therapies, summarizing their current status and near-term potential for translation.

  View details for DOI 10.1016/j.ymthe.2021.10.001

  View details for PubMedID 34673274

• PET reporter gene imaging and ganciclovir-mediated ablation of chimeric antigen receptor T-cells in solid tumors. Cancer research Murty, S., Labanieh, L., Murty, T., Gowrishankar, G., Haywood, T., Alam, I. S., Beinat, C., Robinson, E., Aalipour, A., Klysz, D. D., Cochran, J. R., Majzner, R. G., Mackall, C. L., Gambhir, S. S. 2020

  Abstract

  Imaging strategies to monitor chimeric antigen receptor (CAR) T-cell biodistribution and proliferation harbor the potential to facilitate clinical translation for the treatment of both liquid and solid tumors. Additionally, the potential adverse effects of CAR T-cells highlight the need for mechanisms to modulate CAR T-cell activity. The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene has previously been translated as a positron emission tomography (PET) reporter gene for imaging of T-cell trafficking in brain tumor patients. The HSV1-TK enzyme can act as a suicide gene of transduced cells through treatment with the prodrug ganciclovir (GCV). Here we report the molecular engineering, imaging, and GCV-mediated destruction of B7H3 CAR T-cells incorporating a mutated version of the HSV1-tk gene (sr39tk) with improved enzymatic activity for GCV. The sr39tk gene did not affect B7H3 CAR T-cell functionality and in vitro and in vivo studies in osteosarcoma models showed no significant effect on B7H3 CAR T-cell antitumor activity. PET/CT imaging with 9-(4-[18F]-fluoro-3-[hydroxymethyl]butyl)guanine [18F]FHBG of B7H3-sr39tk CAR T-cells in an orthotopic model of osteosarcoma revealed tumor homing and systemic immune expansion. Bioluminescence and PET imaging of B7H3-sr39tk CAR T-cells confirmed complete tumor ablation with intraperitoneal GCV administration. This imaging and suicide ablation system can provide insight into CAR T-cell migration and proliferation during clinical trials while serving as a suicide switch to limit potential toxicities.

  View details for DOI 10.1158/0008-5472.CAN-19-3579

  View details for PubMedID 32958548

• Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model Oncoimmunology Murty, S., Haile, S. T., Beinat, C., Aalipour, A., Alam, I. S., Murty, T., Shaffer, T. M., Patel, C. B., Graves, E. E., Mackall, C. L., Gambhir, S. S. 2020; 9 (1)

  View details for DOI 10.1080/2162402X.2020.1757360