IL-15 Superagonist Complex ALT-803

  • New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity. Bailey CP, Budak-Alpdogan T, Sauter CT, Panis MM, Buyukgoz C, Jeng EK, Wong HC, Flomenberg N, Alpdogan O. Oncotarget, 2017 May 15. doi: 10.18632/oncotarget.17875. [Epub ahead of print]
  • Intravesical ALT-803 for BCG-unresponsive Bladder Cancer – A Case Report. Huang J, Schisler J, Wong HC, Rosser CJ, Sterbis J. Urol Case Rep. 2017 Jun 8;14:15-17.
  • IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Felices M, Chu S, Kodal B, Bendzick L, Ryan C, Lenvik AJ, Boylan KL, Wong HC, Skubitz AP, Miller JS, Geller MA. Gynecol Oncol. 2017 Jun;145(3):453-461.
  • A Novel Fusion of ALT-803 (Interleukin (IL)-15 Superagonist) with an Antibody Demonstrates Antigen-specific Antitumor Responses. Liu B, Kong L, Han K, Hong H, Marcus WD, Chen X, Jeng EK, Alter S, Zhu X, Rubinstein MP, Shi S, Rhode PR, Cai W, Wong HC. J Biol Chem. 2016 Nov 11;291(46):23869-23881.
  • The immunomodulatory, antitumor and antimetastatic responses of melanoma-bearing normal and alcoholic mice to sunitinib and ALT-803: a combinatorial treatment approach. Gaither KA, Little AA, McBride AA, Garcia SR, Brar KK, Zhu Z, Platt A, Zhang F, Meadows GG, Zhang H. Cancer Immunol Immunother. 2016 Sep;65(9):1123-34.
  • IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors. Allegrezza MJ, Rutkowski MR, Stephen TL, Svoronos N, Tesone AJ, Perales-Puchalt A, Nguyen JM, Sarmin F, Sheen MR, Jeng EK, Tchou J, Wong HC, Fiering SN, Conejo-Garcia JR. Cancer Res. 2016 May 1;76(9):2561-72.
  • A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes. Jones RB, Mueller S, O’Connor R, Rimpel K, Sloan DD, Karel D, Wong HC, Jeng EK, Thomas AS, Whitney JB, Lim SY, Kovacs C, Benko E, Karandish S, Huang SH, Buzon MJ, Lichterfeld M, Irrinki A, Murry JP, Tsai A, Yu H, Geleziunas R, Trocha A, Ostrowski MA, Irvine DJ, Walker BD. PLoS Pathog. 2016 Apr 15;12(4):e1005545.
  • IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas. Kim PS, Kwilas AR, Xu W, Alter S, Jeng EK, Wong HC, Schlom J, Hodge JW. Oncotarget. 2016 Mar 29;7(13):16130-45.
  • The IL-15-Based ALT-803 Complex Enhances FcγRIIIa-Triggered NK Cell Responses and In Vivo Clearance of B Cell Lymphomas. Rosario M, Liu B, Kong L, Collins LI, Schneider SE, Chen X, Han K, Jeng EK, Rhode PR, Leong JW, Schappe T, Jewell BA, Keppel CR, Shah K, Hess B, Romee R, Piwnica-Worms DR, Cashen AF, Bartlett NL, Wong HC, Fehniger TA. Clin Cancer Res. 2016 Feb 1;22(3):596-608.
  • Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models. Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, Liu B, Zhu X, Wen J, You L, Kong L, Edwards AC, Han K, Shi S, Alter S, Sacha JB, Jeng EK, Cai W, Wong HC. Cancer Immunol Res. 2016 Jan;4(1):49-60.
  • Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC. Basher F, Jeng EK, Wong H, Wu J. Oncotarget. 2016 Jan 5;7(1):814-30.
  • Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model. Mathios D, Park CK, Marcus WD, Alter S, Rhode PR, Jeng EK, Wong HC, Pardoll DM, Lim M. Int J Cancer. 2016 Jan 1;138(1):187-94.
  • In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice. Seay K, Church C, Zheng JH, Deneroff K, Ochsenbauer C, Kappes JC, Liu B, Jeng EK, Wong HC, Goldstein H. J Virol. 2015 Jun;89(12):6264-74.
  • Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes. Jones RB, O’Connor R, Mueller S, Foley M, Szeto GL, Karel D, Lichterfeld M, Kovacs C, Ostrowski MA, Trocha A, Irvine DJ, Walker BD. PLoS Pathog. 2014 Aug 14;10(8):e1004287.
  • Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion. Gomes-Giacoia E, Miyake M, Goodison S, Sriharan A, Zhang G, You L, Egan JO, Rhode PR, Parker AS, Chai KX, Wong HC, Rosser CJ. PLoS One. 2014 Jun 4;9(6):e96705.
  • The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8+ T cells into innate-like effector cells with antitumor activity. Wong HC, Jeng EK, Rhode PR. Oncoimmunology. 2013 Nov 1;2(11):e26442.
  • Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 ReceptorαSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma. Xu W, Jones M, Liu B, Zhu X, Johnson CB, Edwards AC, Kong L, Jeng EK, Han KP, Marcus WD, Rubinstein MP, Rhode PR, Wong HC. Cancer Res. 2013 May 15;73(10): 3075-86.
  • Taming Difficult to Express Proteins. Angelo DePalma. Genetic Engineering & Biotechnology News. June 15, 2012, 32(12): 1-41.
  • IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, Vyas VV, Marcus WD, Chavaillaz PA, Romero CA, Rhode PR, Wong HC. Cytokine. 2011 Dec;56(3):804-10.
  • Interleukin-15:Interleukin-15 receptor α scaffold for creation of multivalent targeted immune molecules. Wong RL, Liu B, Zhu X, You L, Kong L, Han KP, Lee HI, Chavaillaz PA, Jin M, Wang Y, Rhode PR, Wong HC. Protein Eng Des Sel. 2011 Apr;24(4):373-83.
  • Novel human interleukin-15 agonists. Zhu X, Marcus WD, Xu W, Lee HI, Han K, Egan JO, Yovandich JL, Rhode PR, Wong HC. J Immunol. 2009 Sep 15;183(6):3598-607.

Human Tissue Factor Antibodies and Antagonists

  • ImmunoPET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer with a Dual-Labeled Bispecific Antibody Fragment. Luo H, England CG, Goel S, Graves SA, Ai F, Liu B, Theuer CP, Wong HC, Nickles RJ, Cai W. Mol Pharm. 2017 May 1;14(5):1646-1655.
  • Tissue factor-specific ultra-bright SERRS nanostars for Raman detection of pulmonary micrometastases. Nayak TR, Andreou C, Oseledchyk A, Marcus WD, Wong HC, Massagué J, Kircher MF. Nanoscale. 2017 Jan 19;9(3):1110-1119.
  • ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment. Shi S, Hong H, Orbay H, Graves SA, Yang Y, Ohman JD, Liu B, Nickles RJ, Wong HC, Cai W. Eur J Nucl Med Mol Imaging. 2015 Jul;42(8):1295-303.
  • Immuno-PET of tissue factor in pancreatic cancer. Hong H, Zhang Y, Nayak TR, Engle JW, Wong HC, Liu B, Barnhart TE, Cai W. J Nucl Med. 2012 Nov;53(11):1748-54.
  • A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome. Morris PE, Steingrub JS, Huang BY, Tang S, Liu PM, Rhode PR, Wong HC. BMC Pulm Med. 2012 Feb 16;12:5.
  • Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site. Jiao JA, Kelly AB, Marzec UM, Nieves E, Acevedo J, Burkhardt M, Edwards A, Zhu XY, Chavaillaz PA, Wong A, Wong JL, Egan JO, Taylor D, Rhode PR, Wong HC. Thromb Haemost. 2010 Jan;103(1):224-33.
  • Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure. Welty-Wolf KE, Carraway MS, Ortel TL, Ghio AJ, Idell S, Egan J, Zhu X, Jiao JA, Wong HC, Piantadosi CA. Am J Physiol Lung Cell Mol Physiol. 2006 Jan;290(1):L21-31.
  • Highly efficient transient expression of functional recombinant antibodies in lettuce. Negrouk V, Eisner G, Lee H, Han K, Taylor D, Wong HC. Plant Science 2005;169:433438.
  • Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial. Morrow DA, Murphy SA, McCabe CH, Mackman N, Wong HC, Antman EM. Eur Heart J. 2005 Apr;26(7):682-8.

ALT-801 and Soluble T-cell Receptor (STARTM) Technology

  • Phase I trial of ALT-801, an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Fishman MN, Thompson JA, Pennock GK, Gonzalez R, Diez LM, Daud AI, Weber JS, Huang BY, Tang S, Rhode PR, Wong HC. Clin Cancer Res. 2011 Dec 15;17(24):7765-75.
  • In vivo imaging of T cell priming. Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN, Zheng H, Peixoto A, Flynn M, Senman B, Junt T, Wong HC, Chakraborty AK, von Andrian UH. Sci Signal. 2008 Mar 25;1(12):pt2.
  • T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN, Zheng H, Peixoto A, Flynn MP, Senman B, Junt T, Wong HC, Chakraborty AK, von Andrian UH. Nat Immunol. 2008 Mar;9(3):282-91.
  • Targeting activity of a TCR/IL-2 fusion protein against established tumors. Wen J, Zhu X, Liu B, You L, Kong L, Lee HI, Han KP, Wong JL, Rhode PR, Wong HC. Cancer Immunol Immunother. 2008 Dec;57(12):1781-94.
  • Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein. Belmont HJ, Price-Schiavi S, Liu B, Card KF, Lee HI, Han KP, Wen J, Tang S, Zhu X, Merrill J, Chavillaz PA, Wong JL, Rhode PR, Wong HC. Clin Immunol. 2006 Oct;121(1):29-39.
  • Visualization of p53(264-272)/HLA-A*0201 complexes naturally presented on tumor cell surface by a multimeric soluble single-chain T cell receptor. Zhu X, Belmont HJ, Price-Schiavi S, Liu B, Lee HI, Fernandez M, Wong RL, Builes J, Rhode PR, Wong HC. J Immunol. 2006 Mar 1;176(5):3223-32.
  • In vitro and in vivo characterization of a novel antibody-like single-chain TCR human IgG1 fusion protein. Mosquera LA, Card KF, Price-Schiavi SA, Belmont HJ, Liu B, Builes J, Zhu X, Chavaillaz PA, Lee HI, Jiao JA, Francis JL, Amirkhosravi A, Wong RL, Wong HC. J Immunol. 2005 Apr 1;174(7):4381-8.
  • A soluble single-chain T-cell receptor IL-2 fusion protein retains MHC-restricted peptide specificity and IL-2 bioactivity. Card KF, Price-Schiavi SA, Liu B, Thomson E, Nieves E, Belmont H, Builes J, Jiao JA, Hernandez J, Weidanz J, Sherman L, Francis JL, Amirkhosravi A, Wong HC. Cancer Immunol Immunother. 2004 Apr;53(4):345-57.
  • Display of functional alphabeta single-chain T-cell receptor molecules on the surface of bacteriophage. Weidanz JA, Card KF, Edwards A, Perlstein E, Wong HC. J Immunol Methods. 1998 Dec 1;221(1-2):59-76.
  • Single-chain MHC class II molecules induce T cell activation and apoptosis. Rhode PR, Burkhardt M, Jiao J, Siddiqui AH, Huang GP, Wong HC. J Immunol. 1996 Dec 1;157(11):4885-91.
Used with permission of the AACR. Originally published as the cover of Cancer Immunology Research.

Rhode PR, et al. Cancer Immunol Res. 2016 Jan;4(1):49-60.