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Daniel  Abate-Daga

Daniel Abate-Daga, PhD

Program: Immunology

Research Program: Immuno-Oncology Program

Contact

  • Overview

    The effort in Dr. Abate Daga's lab spans a wide process: starting with the identification of tumor-associated antigens, generation of the appropriate targeting receptor for genetic modification of T cells, in vitro and in vivo validation of immune receptors, and, ultimately, the implementation of those treatments in phase I clinical trials.

    Associations

    • Immunology
    • Cutaneous Oncology
    • Cutaneous Oncology
    • Immunology
    • Gastrointestinal Oncology
    • Immuno-Oncology Program
    • Melanoma & Skin Cancer Center of Excellence
    • Lung Cancer Center of Excellence

    Education & Training

    Graduate:

    • Center for Genomic Regulation and Pompeu Fabra University, PhD - Molecular Biology-Cancer Gene Therapy

    Fellowship:

    • National Cancer Institute - Surgery
  • Research Interest

    Dr. Abate-Daga's research is focused on the development of T cell-based immunotherapies for the treatment of cancer, and the translation of those preclinical findings into clinical application. The effort in my lab spans a wide process: starting with the identification of tumor-associated antigens, generation of the appropriate targeting receptor for genetic modification of T cells, in vitro and in vivo validation of immune receptors, and, ultimately, the implementation of those treatments in phase I clinical trials. A special emphasis is put on the use of gene therapy technologies, involving the expression of chimeric antigen receptors (CAR) and traditional T-cell receptors (TCR) to "train" the patient's own immune system to detect and kill cancer cells. The gene transfer of immune receptors is accomplished by retroviral transduction of primary human lymphocytes, and has proven efficacious in the induction of clinical remissions of patients with B cell malignancies. Beyond its therapeutic potential, this technology can be used in the laboratory setting to pursue basic scientific research leading to a better understanding of tumor and immune cell biology. Active and prospective projects in the laboratory include the study of antigen recognition, by tumor-infiltrating T cells from pancreatic cancer, bladder cancer and melanoma, geared towards the isolation of TCRs that recognize cancer/testis antigens of therapeutic interest. In parallel, CARs with specificity for IL13RA2 (melanoma, glioma, cervical cancer), TLR2, ABCC3 (pancreatic cancer) and FGFR3 (bladder cancer) are part of the developmental pipeline. Finally, a basic study of the physical and functional interactions of CARs with endogenous T cell molecules will be performed, utilizing gene expression, protein biochemistry and high throughput phosphopeptidome analyses. From this project, Dr. Abate-Daga expects to gain insight into the structure-function correlates associated with different CAR designs; with the ultimate goal of learning how to design safer and more potent receptors for therapy.  

  • Publications

    • Hall MS, Teer JK, Yu X, Branthoover H, Snedal S, Rodriguez-Valentin M, Nagle L, Scott E, Schachner B, Innamarato P, Hall AM, Blauvelt J, Rich CJ, Richards AD, Ceccarelli J, Langer TJ, Yoder SJ, Beatty MS, Cox CA, Messina JL, Abate-Daga D, Mule JJ, Mullinax JE, Sarnaik AA, Pilon-Thomas S. Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients. J Immunother Cancer. 2023 Oct.11(10). Pubmedid: 37802604. Pmcid: PMC10565316.
    • Frieling JS, Tordesillas L, Bustos XE, Ramello MC, Bishop RT, Cianne JE, Snedal SA, Li T, Lo CH, de la Iglesia J, Roselli E, Benzaïd I, Wang X, Kim Y, Lynch CC, Abate-Daga D. γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer. Sci Adv. 2023 May.9(18):eadf0108. Pubmedid: 37134157. Pmcid: PMC10156127.
    • Potez M, Snedal S, She C, Kim J, Thorner K, Tran TH, Ramello MC, Abate-Daga D, Liu JKC. Use of phage display biopanning as a tool to design CAR-T cells against glioma stem cells. Front Oncol. 2023 Mar.13:1124272. Pubmedid: 37035164. Pmcid: PMC10080078.
    • Dukes CW, Rossetti RA, Hensel JA, Snedal S, Cubitt CL, Schell MJ, Abrahamsen M, Isaacs-Soriano K, Kennedy K, Mangual LN, Whiting J, Martinez-Brockhus V, Islam JY, Rathwell J, Beatty M, Hall AM, Abate-Daga D, Giuliano AR, Pilon-Thomas S. SARS-CoV-2 antibody response duration and neutralization following natural infection. J Clin Virol Plus. 2023 Aug.3(3). Pubmedid: 37654784. Pmcid: PMC10470471.
    • Mandriani B, Pellè E, Mannavola F, Palazzo A, Marsano RM, Ingravallo G, Cazzato G, Ramello MC, Porta C, Strosberg J, Abate-Daga D, Cives M. Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors. J Immunother Cancer. 2022 Jun.10(6). Pubmedid: 35764366. Pmcid: PMC9240886.
    • Bustos X, Snedal S, Tordesillas L, Pelle E, Abate-Daga D. γδ T Cell-Based Adoptive Cell Therapies Against Solid Epithelial Tumors. Cancer J. 2022 Jul.28(4):270-277. Pubmedid: 35880936. Pmcid: PMC9335899.
    • Vasic D, Lee JB, Leung Y, Khatri I, Na Y, Abate-Daga D, Zhang L. Allogeneic double-negative CAR-T cells inhibit tumor growth without off-tumor toxicities. Sci Immunol. 2022 Apr.7(70):eabl3642. Pubmedid: 35452255.
    • Mandriani B, Pelle' E, Pezzicoli G, Strosberg J, Abate-Daga D, Guarini A, Cives M, Porta C. Adoptive T-cell immunotherapy in digestive tract malignancies: Current challenges and future perspectives. Cancer Treat Rev. 2021 Nov.100:102288. Pubmedid: 34525422.
    • Van Vliet A, Girardot A, Bouchez J, Bigness A, Wang K, Moino D, Theodotou A, Pothuraju T, Felder S, Smith P, Kumar A, Dayicioglu D. How Big Is Too Big?: The Effect of Defect Size on Postoperative Complications of Vertical Rectus Abdominis Flap Reconstruction. Ann Plast Surg. 2021 Jun.86(6S Suppl 5):S571-S574. Pubmedid: 34100815.
    • Kirtane K, Elmariah H, Chung CH, Abate-Daga D. Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead. J Immunother Cancer. 2021 Jul.9(7). Pubmedid: 34301811. Pmcid: PMC8311333.
    • Li D, Li N, Zhang YF, Fu H, Feng M, Schneider D, Su L, Wu X, Zhou J, Mackay S, Kramer J, Duan Z, Yang H, Kolluri A, Hummer AM, Torres MB, Zhu H, Hall MD, Luo X, Chen J, Wang Q, Abate-Daga D, Dropublic B, Hewitt SM, Orentas RJ, Greten TF, Ho M. Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice. Gastroenterology. 2020 Jun.158(8):2250-2265.e20. Pubmedid: 32060001. Pmcid: PMC7282931.
    • Heidbuechel JPW, Abate-Daga D, Engeland CE, Enderling H. Mathematical Modeling of Oncolytic Virotherapy. Methods Mol Biol. 2019 Sep.2058:307-320. Pubmedid: 31486048.
    • Roselli E, Frieling JS, Thorner K, Ramello MC, Lynch CC, Abate-Daga D. CAR-T Engineering: Optimizing Signal Transduction and Effector Mechanisms. BioDrugs. 2019 Sep.33(6):647-659. Pubmedid: 31552606.
    • Eroglu Z, Holmen SL, Chen Q, Khushalani NI, Amaravadi R, Thomas R, Ahmed KA, Tawbi H, Chandra S, Markowitz J, Smalley I, Liu JKC, Ann Chen Y, Najjar YG, Karreth FA, Abate-Daga D, Glitza IC, Sosman JA, Sondak VK, Bosenberg M, Herlyn M, Atkins MB, Kluger H, Margolin K, Forsyth PA, Davies MA, Smalley KSM. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell Melanoma Res. 2019 May.32(3):458-469. Pubmedid: 30712316. Pmcid: PMC7771318.
    • Ramello MC, Benzaïd I, Kuenzi BM, Lienlaf-Moreno M, Kandell WM, Santiago DN, Pabón-Saldaña M, Darville L, Fang B, Rix U, Yoder S, Berglund A, Koomen JM, Haura EB, Abate-Daga D. An immunoproteomic approach to characterize the CAR interactome and signalosome. Sci Signal. 2019 Feb.12(568). Pubmedid: 30755478. Pmcid: PMC6506216.
    • Schacht C, Meade A, Banks HT, Enderling H, Abate-Daga D. Estimation of probability distributions of parameters using aggregate population data: analysis of a CAR T-cell cancer model. Math Biosci Eng. 2019 Aug.16(6):7299-7326. Pubmedid: 31698614.
    • Li G, Boucher JC, Kotani H, Park K, Zhang Y, Shrestha B, Wang X, Guan L, Beatty N, Abate-Daga D, Davila ML. 4-1BB enhancement of CAR T function requires NF-κB and TRAFs. JCI Insight. 2018 Sep.3(18). Pubmedid: 30232281. Pmcid: PMC6237232.
    • Forsyth PA, Abate-Daga D. Viral Therapy Gets Personal: A Potential Gene Signature to Predict Susceptibility to Measles Virus Oncolysis. J Natl Cancer Inst. 2018 Oct.110(10):1139-1140. Pubmedid: 29757401.
    • Forsyth PA, Abate-Daga D. Oncolytic Virotherapy for Malignant Gliomas. J Clin Oncol. 2018 May.36(14):1440-1442. Pubmedid: 29437534.
    • Ramello MC, Haura EB, Abate-Daga D. CAR-T cells and combination therapies: What's next in the immunotherapy revolution?. Pharmacol Res. 2018 Mar.129:194-203. Pubmedid: 29203440. Pmcid: PMC5828987.
    • Abate-Daga D, Ramello MC, Smalley I, Forsyth PA, Smalley KSM. The biology and therapeutic management of melanoma brain metastases. Biochem Pharmacol. 2018 Jul.153:35-45. Pubmedid: 29278675. Pmcid: PMC5959746.
    • Santiago DN, Heidbuechel JPW, Kandell WM, Walker R, Djeu J, Engeland CE, Abate-Daga D, Enderling H. Fighting Cancer with Mathematics and Viruses. Viruses. 2017 Aug.9(9). Pubmedid: 28832539. Pmcid: PMC5618005.
    • Khanna S, Thomas A, Abate-Daga D, Zhang J, Morrow B, Steinberg SM, Orlandi A, Ferroni P, Schlom J, Guadagni F, Hassan R. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab. J Thorac Oncol. 2016 Nov.11(11):1993-2005. Pubmedid: 27544053. Pmcid: PMC5075512.
    • Abate-Daga D, Davila ML. CAR models: next-generation CAR modifications for enhanced T-cell function. Mol Ther Oncolytics. 2016 May.3:16014. Pubmedid: 27231717. Pmcid: PMC4871190.
    • Beane JD, Lee G, Zheng Z, Mendel M, Abate-Daga D, Bharathan M, Black M, Gandhi N, Yu Z, Chandran S, Giedlin M, Ando D, Miller J, Paschon D, Guschin D, Rebar EJ, Reik A, Holmes MC, Gregory PD, Restifo NP, Rosenberg SA, Morgan RA, Feldman SA. Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma. Mol Ther. 2015 Aug.23(8):1380-1390. Pubmedid: 25939491. Pmcid: PMC4817870.
    • Park TS, Abate-Daga D, Zhang L, Zheng Z, Morgan RA. Gamma-retroviral vector design for the co-expression of artificial microRNAs and therapeutic proteins. Nucleic Acid Ther. 2014 Oct.24(5):356-363. Pubmedid: 25019196. Pmcid: PMC4162432.
    • Abate-Daga D, Speiser DE, Chinnasamy N, Zheng Z, Xu H, Feldman SA, Rosenberg SA, Morgan RA. Development of a T cell receptor targeting an HLA-A*0201 restricted epitope from the cancer-testis antigen SSX2 for adoptive immunotherapy of cancer. PLoS One. 2014 Mar.9(3):e93321. Pubmedid: 24681846. Pmcid: PMC3969312.
    • Abate-Daga D, Rosenberg SA, Morgan RA. Pancreatic cancer: Hurdles in the engineering of CAR-based immunotherapies. Oncoimmunology. 2014 Jun.3:e29194. Pubmedid: 25083334. Pmcid: PMC4108460.
    • Abate-Daga D, Lagisetty KH, Tran E, Zheng Z, Gattinoni L, Yu Z, Burns WR, Miermont AM, Teper Y, Rudloff U, Restifo NP, Feldman SA, Rosenberg SA, Morgan RA. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther. 2014 Dec.25(12):1003-1012. Pubmedid: 24694017. Pmcid: PMC4270113.
    • Beard RE, Zheng Z, Lagisetty KH, Burns WR, Tran E, Hewitt SM, Abate-Daga D, Rosati SF, Fine HA, Ferrone S, Rosenberg SA, Morgan RA. Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells. J Immunother Cancer. 2014 Aug.2:25. Pubmedid: 25197555. Pmcid: PMC4155770.
    • Rosati SF, Parkhurst MR, Hong Y, Zheng Z, Feldman SA, Rao M, Abate-Daga D, Beard RE, Xu H, Black MA, Robbins PF, Schrump DA, Rosenberg SA, Morgan RA. A novel murine T-cell receptor targeting NY-ESO-1. J Immunother. 2014 Apr.37(3):135-146. Pubmedid: 24598449. Pmcid: PMC7443746.
    • Beard RE, Abate-Daga D, Rosati SF, Zheng Z, Wunderlich JR, Rosenberg SA, Morgan RA. Gene expression profiling using nanostring digital RNA counting to identify potential target antigens for melanoma immunotherapy. Clin Cancer Res. 2013 Sep.19(18):4941-4950. Pubmedid: 24021875. Pmcid: PMC3778100.
    • Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother. 2013 Feb.36(2):133-151. Pubmedid: 23377668. Pmcid: PMC3581823.
    • Abate-Daga D, Hanada K, Davis JL, Yang JC, Rosenberg SA, Morgan RA. Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood. 2013 Aug.122(8):1399-1410. Pubmedid: 23861247. Pmcid: PMC3750338.
    • Abate-Daga D, Andreu N, Camacho-Sánchez J, Alemany R, Herance R, Millán O, Fillat C. Oncolytic adenoviruses armed with thymidine kinase can be traced by PET imaging and show potent antitumoural effects by ganciclovir dosing. PLoS One. 2012 Feb.6(10):e26142. Pubmedid: 22028820. Pmcid: PMC3196510.
    • Garcia-Rodríguez L, Abate-Daga D, Rojas A, González JR, Fillat C. E-cadherin contributes to the bystander effect of TK/GCV suicide therapy and enhances its antitumoral activity in pancreatic cancer models. Gene Ther. 2011 Jan.18(1):73-81. Pubmedid: 20720574.
    • Abate-Daga D, Garcia-Rodríguez L, Sumoy L, Fillat C. Cell cycle control pathways act as conditioning factors for TK/GCV sensitivity in pancreatic cancer cells. Biochim Biophys Acta. 2010 Oct.1803(10):1175-1185. Pubmedid: 20599444.
    • Cascante A, Abate-Daga D, Garcia-Rodríguez L, González JR, Alemany R, Fillat C. GCV modulates the antitumoural efficacy of a replicative adenovirus expressing the Tat8-TK as a late gene in a pancreatic tumour model. Gene Ther. 2007 Oct.14(20):1471-80. Pubmedid: 17713568.
    • Guglielmone HA, Minoldo S, Jarchum GD, Daga DA, Bocco JL. Fibrinogen Cordoba I: A gammaArg 275 His substitution associated with defective polymerization. Thromb Res. 2007 Jan.121(3):429-30. Pubmedid: 17604827.
    • Huch M, Abate-Daga D, Roig JM, González JR, Fabregat J, Sosnowski B, Mazo A, Fillat C. Targeting the CYP2B 1/cyclophosphamide suicide system to fibroblast growth factor receptors results in a potent antitumoral response in pancreatic cancer models. Hum Gene Ther. 2006 Dec.17(12):1187-1200. Pubmedid: 17069538.
    • Desmarchelier C, del V Pacciaroni A, Abate-Daga D, Coussio J, Gil RR, Silva GL. Antioxidant and free radical scavenging activities of Misodendrum punctulatum, myzodendrone and structurally related phenols. Phytother Res. 2005 Dec.19(12):1043-1047. Pubmedid: 16372370.
    • Guglielmone HA, Sanchez MC, Abate Daga D, Bocco JL. A new heterozygous mutation in gamma fibrinogen gene leading to 326 Cys-->Ser substitution in fibrinogen Córdoba is associated with defective polymerization and familial hypodysfibrinogenemia. J Thromb Haemost. 2004 Feb.2(2):352-4. Pubmedid: 14996011.
  • Grants

    • Title: Targeting Tumor Microenvironment to Improve TIL Expansion in Lung and Bladder Tumors
      Sponsor: Moffitt Fdtn
      PI: Beatty, M., CO-PI: Abate-Daga, D.
    • Title: KIR2DL2 Immune Checkpoint as Modulator of T-Cell Effector Function
      Sponsor: Nat Institutes of Health
      PI: Abate-Daga, D.
    • Title: Understanding the influence of bone-metastatic prostate cancer and mesenchymal stromal cells on γδ T cells, in the bone microenvironment.
      Sponsor: Nat Institutes of Health
      PI (Contact): Abate-Daga, D.

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