Molecular and Cellular Therapy

Osvaldo L. Podhajcer - Fundación Instituto Leloir

Language:

The laboratory is a reference in advanced medicines designed from oncolytic virus engineering. One of our developments is on track to initiate clinical trials in humans. These genetically-based drugs can be combined with treatments commonly used in cancer. We also work hard in the use of stem cells coupled to viruses and in the design of nanodrugs combining genetically based drugs with chemicals. Together with the Genocan unit we have a strong anchoring in the area of ​​precision medicine in genomics of human breast cancer, in colorectal cancer and in oncopediatrics. The group had and has collaborations, in some cases more than 10 years, with various hospitals such as the María Curie of Oncology, the Eva Perón de San Martín, the Roffo Institute of CABA, the Garrahan National Pediatrics Hospital, the Udaondo, the Naval Hospital and the Churruca of CABA.
Oncolytic immunotherapy is based on viral-based drugs administered for a direct attack on the tumor, followed by a secondary immune response stimulated by genes included in the viruses. This is the only type of therapy that works as a therapeutic drug and vaccine at the same time. The group has a strong track record in the design and use of Oncolytic Adenoviruses (OAV) for cancer. We combine the use of OAVs with modified mesenchymal stem cells with artificial receptors of our own design and we direct them towards the tumor using single domain antibodies obtained from camelids. In nanomedicine we develop nanofármacos (combining genetically based drugs with chemotherapy) that are directed through the use of antibodies. For this we have generated libraries of antibodies directed against antigens associated with malignant cells. In Genomics and Precision Medicine, we are part of the United States-Latin American Cancer Reserach Network (US-LACRN), coordinated by the Center for Global Health of the National Cancer Institute of the USA, whose objectives are to identify molecular signatures that improve the prognosis of the evolution of breast cancer and predict the response to neoadjuvant chemotherapy. We also led a local consortium to identify signatures that could predict the response to radiochemotherapy in rectal cancer. Our works include studies in oncopediatrics.

González-Pastor R, Ashshi AM, El-Shemi AG, Dmitriev IP, Kashentseva EA, Lu ZH, Goedegebuure SP, Podhajcer OL, Curiel DT. Defining a murine ovarian cancer model for the evaluation of conditionally-replicative adenovirus (CRAd) virotherapy agents. J Ovarian Res. 2019 Feb 15;12(1):18

Iezzi ME, Policastro L, Werbajh S, Podhajcer OL#, Canziani GA#.  Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment. Front Immunol. 2018 Feb 19;9:273. doi: 10.3389/fimmu.2018.00273.# Shared senior authorship.

Cafferata EG, Lopez MV, Nuñez FJ, Maenza MAR, Podhajcer OL. Application of Synthetic Tumor-Specific Promoters Responsive to the Tumor Microenvironment. Methods Mol Biol. 2017;1651:213-227. doi: 10.1007/978-1-4939-7223-4_16

Lopez MV, Cafferata EG, Viale DL, Podhajcer OL. Synthetic Tumor-Specific Promoters for Transcriptional Regulation of Viral Replication. Methods Mol Biol. 2017;1651:113-130. doi: 10.1007/978-1-4939-7223-4_9.

Ana Laura Alfano, Alejandro Nicola Candia, Nicasio Cuneo, Leandro N. Guttlein, Alejandro Soderini, Cecilia Rotondaro, Leonardo Sganga, Osvaldo L. Podhajcer and M. Veronica Lopez. Oncolytic adenovirus-loaded 1 Menstrual Blood Stem Cells overcome the blockade of viral activity exerted by ovary cancer patients’ ascites. Molecular Therapy Oncolytics. 2017 Jun 16;6:31-44. doi: 10.1016/j.omto.2017.06.002. eCollection 2017 Sep 15.

Merino, Gabriela; Murua, Yanina; Fresno Rodríguez, Cristóbal; Sendoya, Juan; Golubicki, Mariano; Iseas, Soledad; Coraglio, Mariana; Podhajcer, Osvaldo; Llera, Andrea; Fernández, Elmer. TarSeqQC: Quality Control on Targeted Sequencing Experiments in R. Human Mutation. Hum Mutat. 2017 May;38(5):494-502.

Cristóbal Fresno , Germán Alexis González, Gabriela Alejandra Merino, Ana Georgina Flesia, Osvaldo Luis Podhajcer, Andrea Sabina Llera and Elmer Andrés Fernández. A novel non-parametric method for uncertainty evaluation of correlation-based molecular signatures: its application on PAM50 algorithm ioinformatics doi.10.1093/bioinformatics, en prensa

Leandro N. Guttlein, Lorena G. Benedetti, Cristobal Fresno, Raul G. Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L. Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A. Fernandez, Vanessa Gottifredi, Norberto W. Zwirner, Andrea S. Llera and Osvaldo L Podhajcer. Predictive outcomes for HER2-enriched cancer using growth and metastasis signatures driven by SPARC. Mol Cancer Res. 2016 Dec 28. pii: molcanres.0243.2016. doi: 10.1158/1541-7786.MCR-16-0243-T. [Epub ahead of print].

Juriol LV, Gobetto MN, Mendes Garrido Abregú F, Dasso ME, Pineda G, Güttlein L, Carranza A, Podhajcer O, Toblli JE, Elesgaray R, Arranz CT, Tomat AL. Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats. Eur J Nutr. 2016 Nov 7. [Epub ahead of print].

Bayo J, Real A, Fiore EJ, Malvicini M, Sganga L, Bolontrade M, Andriani O, Bizama C, Fresno C, Podhajcer O, Fernandez E, Gidekel M, Mazzolini GD, García MG. IL-8, GRO and MCP-1 produced by hepatocellular carcinoma microenvironment determine the migratory capacity of human bone marrow-derived mesenchymal stromal cells without affecting tumor aggressiveness. Oncotarget. 2016 Jun 25. doi: 10.18632/oncotarget.10288. [Epub ahead of print].

Investigators of the United Sates Latin America Cancer Research Network (Llera AS, Podhajcer OL*, Breitenbach M, Santini L, Muller B, Daneri A, Velazquez C, Gomez J, Frech S, Brown T, Gross T). Translational Research in Cancer Comes of Age in Latin America. Sci Transl Med. 2015 Dec 23;7(319):319fs50. doi: 10.1126/scitranslmed.aad5859. *Corresponding Author





Osvaldo L. Podhajcer
Head of Laboratory - opodhajcer@leloir.org.ar



Andrea Sabrina Llera
Independient Investigator - CONICET



Eduardo Cafferata
Indepentient Investigator - CONICET



María Verónica López
Adjunct Investigator - CONICET



Sabrina Eugenia Vinzón
Assintant Investigator CONICET



Felipe Nuñez
Posdoctoral - CONICET



Juan Martín Sendoya
PhD Fellow - CONICET



Mauro Oscar Heitrich
PhD Fellow - CONICET



Paula Agustina Benegas
PhD Fellow - CONICET



Elvia Carolina Rivas Baquero
PhD Fellow - CONICET



Daiana Ganiewich
Undergraduate Student



Diana Carolina Aguilar Cortés
Undergraduate Student