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Targeted Therapies

Targeted Therapies of CLL and B-Cell Malignancies: Biological, Small Molecule Immunopharmacuetical, Delivery, and MicroRNA

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. The Byrd lab has a long history of innovation and investigating targeted cancer therapies that leverage the immune response. CD19 and IL-21 are examples of novel engineered biological therapies that are developed to enhance antibody therapeutics through direct and immune mediated mechanisms. CD-37-SMIP is a small molecule immune-phamacuetical that promotes antibody-dependent cellular cytotoxicity using a B-cell lineage specific antigen that was previously neglected. Combining research of targeted biological and immunopharmacueticals is leading the way to develop targeted drug delivery using immunonanoparticles. The discovery that the immunosuppressant FTY720 targets phosphatases in leukemia and lymphoma has introduced a new therapeutic target. New collaborations with colleagues at The Ohio State University are investigating the clinical application of microRNAs for therapy.

Selected Papers:

Zhao XB, Lapalombella R, Joshi T, Cheney C, Gowda A, Hayden-Ledbetter MS, Baum PR, Lin TS, Jarjoura D, Lehman A, Kussewitt D, Lee RJ, Caligiuri MA, Tridandapani S, Muthusamy N, Byrd JC. Targeting CD37+ lymphoid malignancies with a novel engineered small modular immunopharmaceutical Blood. 2007 Oct 1;110(7):2569-77

Lapalombella R, Zhao X, Triantafillou G, Yu B, Jin Y, Lozanski G, Cheney C, Heerema N, Jarjoura D, Lehman A, Lee LJ, Marcucci G, Lee RJ, Caligiuri MA, Muthusamy N, Byrd JC. A Novel Raji-Burkitt's Lymphoma Model for Preclinical and Mechanistic Evaluation of CD52-Targeted Immunotherapeutic Agents. Clin Cancer Res. 2008 Jan 15;14(2):569-578

Liu Q, Zhao X, Frissora F, Ma Y, Santhanam R, Jarjoura D, Lehman A, PerrottiD, Chen CS, Dalton JT, Muthusamy N, Byrd JC. FTY720 demonstrates promising pre-clinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphoma. Blood. 2008 Jan 1;111(1):275-84

Liu, Q, Alinari, L, Chen C-S, Yan, F, Dalton J, Lapalombella R, Zhang Xiaoli, Mani R, Lin T, Byrd JC, Baiocchi RA, Muthusamy N. FTY20 Demonstrates Promising In-Vitro and In-vivo Pre-clinical Activity by Down-modulating Cyclin D1 and Phospho-Akt in Mantle Cell Lymphoma. Clin Cancer Res. 2010 Jun 15;16(12):3182-92

Gowda A, Roda J, Hussain SR, Ramanunni A, Joshi T, Schmidt S, Zhang X, Lehman A, Jarjoura D, Kindsvogel W, Cheney C, Caligiuri MA, Tridandapani S, Carson WE, *Muthusamy N, *Byrd JC..IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody dependent cellular cytotoxicity in primary chronic lymphocytic cells. Blood. 2008 May 1;111(9):4723-30

Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J,Yu J Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G. MicroRNA -29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B an indirectly DNMT1 Blood. 2009; 113:6411-6418