Patricia Yotnda, Ph.D.
Department of Medicine
Section of Hematology-Oncology
Baylor College of Medicine
- Ph.D., Immunology, Institute Pasteur, Paris XVII, France
- Postdoctoral Associate, Pediatrics-Hematology/Oncology, Baylor College of Medicine, Houston, TX
Our research interests are Genetic and Cellular anti-tumor vaccines.
We genetically modify immune cells to enable them to home the malignant site and locally deliver therapeutic vectors (e.g adenovirus) or "therapeutic molecules" directly to the abnormal cells. We also investigate the efficiency of cytotoxic T cells in the tumor mass and genetically modify them to increase their viability and function in this unfavorable microenvironment.
We investigate various fiber modified adenovirus vectors to transduce hematopoietic target cells more efficiently and to be able to avoid the effects of the immune response on the gene transfer. We have shown that chimeric fiber adenoviral vectors (Ad5 containing the fiber of a different serotype, different repeats of Polylysine and RGD) transduce hematopoietic stem cells (including SP and ES cells) and also mature cells (B, T, DC, NK cells) in a CAR independent manner. We found that Ad5F35, Polylysine-substituted Ad5F/K21 and peptide-modified Ad5F/RGD are most effective in transducing normal and malignant hematopoietic cells (lymphoma, leukemia etc.).
Cationic liposomes mixed with Ad5 mediate CAR independent gene transfer and was proven to improve transduction efficiency in many tumor models. Moreover, this latter approach allows us to avoid the decrease of therapeutic gene expression, usually induced by the anti-adenovirus immune response in immune animals.
Other projects involve development of replication-competent-adenoviruses engineered to specifically kill tumor but not normal cells and modification of immune cells to enable them to deliver adenoviral vectors directly to tumor cells.
- Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, Heslop HE, Spencer DM, Rooney CM. An inducible caspase 9 safety switch for T-cell therapy. Blood. 2005 Jun 1;105(11):4247-54.
- R. Rangel, JC. Sims-Mourtada, L. Guzman-Rojas, K. Cain, ED. Wieder, JJ. Molldrem, P. Yotnda, C.Guret, V. Francés, D. Bossy, C. Schiff, JN. Wygant, BW. McIntyre, HN. Ananthaswamy, and H. Martinez-Valdez. Assembly of the k PreB receptor requires a Vk - like protein encoded by a germline transcript. J Biol Chem. 2005 May 6;280(18):17807-14.
- P. Yotnda, C. Zompeta, HE. Heslop, M. Andreeff, MK. Brenner, F. Marini. Comparison of the Transduction Efficiency of Hematopoietic Cells with Different Modified Adenoviruses. Hum Gene Ther. 2004 Dec;15(12):1229-42.
- P. Yotnda, N. Charlet, B. Savoldo, C. Rooney, MK. Brenner. Enhanced Antitumor Activity of Specific CTL by Delivery of a Lytic Adenovirus to the Tumor Site. Blood. 2004 Oct 15;104(8):2272-80.
- P. Yotnda, A. Davis, N. Smyth Templeton, MK. Brenner. A New Infectious Circular E1b-deleted-Adenovirus DNA. Mol Ther. 2004 Apr;9(4):489-95.
- J. Duraiswamy, M. Bharadwaj, J. Tellam, G. Connolly, L. Cooper, D. Moss, S. Thomson, P. Yotnda, R. Khanna. Induction of Therapeutic T cell Response to Subdominant Tumor-Associated Viral Oncogene following Immunization with Replication-incompetent Polyepitope Adenovirus Vaccine. Cancer Res. 2004 Feb 15;64(4):1483-1489.
- L. Zou, P. Yotnda, T. Zhao, X. Yuang, A. Kumar, H. Zhou, K. Yang. Extended Transgene Expression Mediated by Helper-Dependent Adenoviral vectors in Traumatically injured Rat Brains. J Cereb Blood Flow Metab. 2002 Aug;22(8):959-70.
- E.A. Olmsted, Z. Gugala, F.H. Gannon, P. Yotnda, R.W. Lindsey, A.R. Davis. Enhanced Bone Formation in vivo Using a Chimeric Adenovirus vector. Hum Gene Ther. 2002 Jul 20;13(11):1337-47G.
- Dotti, B. Salvodo, P. Yotnda, D. Rill, M.K. Brenner. Transgenic expression of CD40L produces an antitumor immune response to both positive and negative multiple myeloma. Blood. July 1, 2002; 100 (1)
- P. Yotnda, T. Dong-Hua Chen, W. Chiu, P. A. Piedra, A. Davis, N. Smyth Templeton, M. K. Brenner. Bilamellar Cationic Liposomes Protect Adenovectors from Pre-existing Humoral Immune Responses. Molecular Therapy. 2002 March 1: 5(3). 233-241.
- P. Yotnda, H. Onishi, HE. Heslop, DM. Shayakhmetov, A. Lieber, MK. Brenner , and. A. Davis. Highly efficient transduction of primitive hematopoietic stem cells by modified Adenovirus. Hum Gene Ther. 2001 Apr 10;12(6):659-70.
- S. Takahashi, P. Yotnda, R. Rousseau, M. Zhuyong, S. Smith, D. Rill, A. Younes, M.k Brenner. STransgenic expression of CD40L and Interleukine-2 induces an autologous anti-tumor response in patients with non Hodgkin lymphoma. Cancer Gene Ther. 2001 May;8(5):378-87.
- S. Takahashi, R. Rousseau, P. Yotnda, M. Zhuyong, G. Dotti, D. Rill, R. Hurwitz, F. Marini, M. Andreeff, M.K Brenner. Autologous Antileukemic Immune Responses Induced by Chronic Lymphocytic leukemia B cells Expressing the CD40 Ligand and Interleukine –2 transgenes. Human Gene Therapy. April 2001: 12 Number: 6 Page: 659 – 670.
- E.A. Olmsted, J.S. Blum, D.Rill, P. Yotnda, Z.Gugala, R.W.Lindsey, A.R.Davis. Adenovirus –Mediated BMP2 Expression in human Bone Marrow Stromal Cell. J Cell Biochem. 2001 Apr 3-27;82(1):11-21.
- Lauvau G, Kakimi K, Niedermann G, Ostankovitch M, Yotnda P, Firat H, Chisari FV, van Endert PM. Human transporters associated with antigen processing (TAPs) select epitope precursor peptides for processing in the endoplasmic reticulum and presentation to T cells. J Exp. Med. 1999 Nov 1;190(9):1227-40.
- Yotnda P, Mintz P, Grigoriadou K, Lemonnier F, Vilmer E, Langlade-Demoyen P. Analysis of T-cell defects in the specific immune response against acute lymphoblastic leukemia cells. Exp. Hematol. 1999 Sep;27(9):1375-83.
- Duval M, Fenneteau O, Doireau V, Faye A, Emilie D, Yotnda P, Drapier JC, Schlegel N, Sterkers G, de Baulny HO, Vilmer E. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr. 1999 Feb;134(2):236-9.
- Yotnda P, Garcia F, Peuchmaur M, Grandchamp B, Duval M, Lemonnier F, Vilmer E, Langlade-Demoyen P.Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia. J Clin Invest. 1998 Jul 15;102(2):455-62.
- Yotnda P, Firat H, Garcia-Pons F, Garcia Z, Gourru G, Vernant JP, Lemonnier FA, Leblond V, Langlade-Demoyen P.Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest. 1998 May 15;101(10):2290-6.
- Duval M, Yotnda P, Bensussan A, Oudhiri N, Guidal C, Rohrlich P, Boumsell L, Grandchamp B, Vilmer E. Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia. Leukemia. 1995.