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- Cutaneous Oncology
Education & Training
- Center for Genomic Regulation and Pompeu Fabra University, PhD - Molecular Biology-Cancer Gene Therapy
- National Cancer Institute, Fellow - Surgery
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.
- 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.
- 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.