Research

CAR T cells

CAR T cells have revolutionized leukemia treatment, but solid tumors present unique challenges. Our lab focuses on next-generation engineering strategies to improve T cell function against the hostile tumor microenvironment. We develop novel Chimeric Antigen Receptors (CARs) that target solid tumor antigens with enhanced specificity. Beyond simple targeting, we can engineer these cells with various payloads like cytokines and co-stimulatory signals to boost their persistence, prevent T cell exhaustion or dysfunction, and allow them to penetrate and kill dense tumor tissues effectively.

Spatial Multi-omics

Tumors are complex ecosystems with distinct cellular neighborhoods. We utilize cutting-edge spatial multi-omics like PhenoCycler-Fusion (formerly known as CODEX) to visuzlize various markers while preserving tissue architecture. This allows us to visualize exactly where various immune cells and CAR T cells traffic within a tumor. We hope to use platforms like these to discover the specific cellular interactions between tumor cells and immune cells to improve our current CAR T therapies.

Viral packaging

The delivery vehicle is just as important as the cargo. Our research dives into the biology of viral vectors (Lentivirus or Retrovirus) to optimize how we manufacture CAR T cells. We investigate methods to modify viral components to improve transduction efficiency, reduce toxicity, and precisely regulate the number of CAR gene copies per cell. By fine-tuning the viral packaging process, we aim to create a safer, more potent, and cost-effective manufacturing pipeline for clinical-grade cell therapies.

Clinical Trials

The ultimate goal of our preclinical research is bedside impact. We are actively leading clinical trials to test the safety and efficacy of our engineered CAR T cell therapies in pediatric and adult patients with relapsed or refractory solid tumors. These trials allow us to assess not just tumor response, but also the safety profile and long-term persistence of our engineered cells in the human body.

Correlative Research

What separates a responder from a non-responder? Correlative biology serves as a bridge between clinical trials and bench science. Our newest branch of research aims to analyze clinical data collected during our trials to better understand clinical outcomes. By studying various clinical variables and the functional status of infused patients, we hope to identify systemic patterns of antitumor efficacy. We hope that this feedback loop will inform the future design of CAR T cell therapies.

Relevant Publications

  • Co-expression of IL15 promotes effector differentiation and sustained proliferative capacity in ALPPL2-specific human CAR T cells

    Cunningham D, Liu J, Cevher Zeytin I, de la Cerda DA, Ghatwai N, Courtney AN, Guo L, Rathi P, Qizhi Yao C, Zhang N, An Z, Heczey AA. Cancer Immunology Research. (2026).

  • Long-term outcomes of GD2-directed CAR-T cell therapy in patients with neuroblastoma.

    Li CH, Sharma S, Heczey AA, Woods ML, Steffin DHM, Louis CU, Grilley BJ, Thakkar SG, Wu M, Wang T, Rooney CM, Brenner MK, Heslop HE. Nat Med. 31(4):1125-1129 (2025).

  • DRIMS: A Synthetic Biology Platform that Enables Deletion, Replacement, Insertion, Mutagenesis, and Synthesis of DNA.

    Caraballo G LD, Cevher Zeytin I, Rathi P, Li CH, Tsao AN, Salvador L YJ, Ranjan M, Traynor BM, Heczey AA. ACS Synth Biol. 14(2):485-496 (2025).

  • Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers

    Steffin D, Ghatwai N, Montalbano A, Rathi P, Courtney AN, Arnett AB, Fleurence J, Sweidan R, Wang T, Zhang H, Masand P, Maris JM, Martinez D, Pogoriler J, Varadarajan N, Thakkar SG, Lyon D, Lapteva N, Zhuyong M, Patel K, Lopez-Terrada D, Ramos CA, Lulla P, Armaghany T, Grilley BJ, Gottschalk S, Dotti G, Metelitsa LS, Heslop HE, Brenner MK, Sumazin P, Heczey A. Nature. 637(8047):940-946 (2025).

  • A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

    Espinoza AF, Patel RH, Patel KR, Badachhape AA, Whitlock R, Srivastava RK, Govindu SR, Duong A, Kona A, Kureti P, Armbruster B, Kats D, Srinivasan RR, Dobrolecki LE, Yu X, Najaf Panah MJ, Zorman B, Sarabia SF, Urbicain M, Major A, Bissig KD, Keller C, Lewis MT, Heczey A, Sumazin P, López-Terrada DH, Woodfield SE, Vasudevan SA. J Hepatol. 80(4):610-621 (2024).

  • Predictive factors and surgical treatment strategy.

    Espinoza AF, Patel KR, Shetty PB, Whitlock RS, Sumazin P, Yu X, Sarabia SF, Urbicain M, Heczey A, Masand P, Woodfield SE, López-Terrada DH, Vasudevan SA. Cancer Med. 12(23):21270-21278 (2023).

  • A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

    Campbell K, Siegel DA, Umaretiya PJ, Dai S, Heczey A, Lupo PJ, Schraw JM, Thompson TD, Scheurer ME, Foster JH. Pediatr Blood Cancer. 71(1):e30732 (2023).

  • Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults.

    Sumazin P, Peters TL, Sarabia SF, Kim HR, Urbicain M, Hollingsworth EF, Alvarez KR, Perez CR, Pozza A, Panah MJN, Epps JL, Scorsone K, Zorman B, Katzenstein H, O'Neill AF, Meyers R, Tiao G, Geller J, Ranganathan S, Rangaswami AA, Woodfield SE, Goss JA, Vasudevan SA, Heczey A, Roy A, Fisher KE, Alaggio R, Patel KR, Finegold MJ, López-Terrada DH. J Hepatol. 13:S0168-8278(22)00275-6 (2022).

  • Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis

    Heczey A, Courtney AN, Montalbano A, Robinson S, Liu K, Li M, Ghatwai N, Dakhova O, Liu B, Raveh-Sadka T, Chauvin-Fleurence CN, Xu X, Ngai H, Di Pierro EJ, Savoldo B, Dotti G, Metelitsa LS. Nature Medicine. 29(6):1379-1388 (2020).