Arap/Pasqualini Laboratory – Timelines and Milestones 12-07-2015


The Human Vascular Mapping Project

  • 2000: Scientific & ethical framework for human experimentation
  • 2002: Combinatorial screening in brain-dead and terminal wean patients (1)
  • 2004: Validation of the IL-11 receptor as a target in prostate cancer (2)
  • 2005: Intra- and inter-institutional ethics guidelines (3, 4)
  • 2006: Design and validation of synchronous experimental approach (5)
  • 2008: Serial synchronous selection adapted for selection in patients (6)
  • 2008: IND filed for a limited Phase 1 clinical trial in prostate cancer patients (NCT00872157)
  • 2009: Translation of a targeted peptidomimetic (BMTP-11) in a first-in-man trial, Protocol 2008-0395
  • 2010: Drug localization established in bone metastasis biopsies in 6 out of 6 patients treated
  • 2010: BMTP-11 licensed to Alvos Therapeutics, a new biotech company (subsidiary of Arrowhead Research).
  • 2010: Patient biopsy and autopsy material processed and captured in a database of more than 2 MM ligands (6)
  • 2011: Over 150 new vascular zip codes identified
  • 2012: Business development opportunities with Pharma leveraging normal and diseased tissue targeting
  • 2015: Publication of the BMTP-11 clinical trial in “Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study” (7)
  • 2015: IL-11 receptor in leukemia and lymphoma in “Targeting interleukin-11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens” (8)
  • 2015: Vasotide inhibition of pathological retinal angiogenesis in the murine retinopathy of prematurity model and non-primate wet age-related macular degeneration (9)


Ligand-directed Targeting, Nanotechnology & Molecular-genetic Imaging

  • 1998-2000:Tumor targeting in preclinical models (10, 11)
  • 2003: Display of combinatorial peptide libraries on AAV particles (12)
  • 2005: Self-assembled biocompatible Au-phage network (13, 14)
  • 2006: AAV-phage (AAVP) for molecular imaging (15, 16)
  • 2008: AAVP predicts drug response in sarcoma: towards an imaging transcriptome (17)
  • 2009: Phase I-II trial of targeted TNF in pet dogs with spontaneous cancer (18)
  • 2010: Integration of the AAVP vector system with other anti-cancer therapies shows synergistic anti-tumor activity (19)
  • 2011: Iron-mimicking peptide in AAVP crosses blood-brain barrier to image and treat glioblastoma (20)
  • 2012: Plans for collaborative work with high-profile sponsors engaged
  • 2012: Technology portfolio captured by AAVP Biosystems
  • 2015: siRNA inhibition of the PCA3/PRUNE2 regulatory axis in prostate cancer (21)


Fingerprinting the Repertoire of Patient-derived Antibodies

  • 2000: Technology design and optimization
  • 2001: Human prostate cancer serum sample selection
  • 2003: Fingerprinting antibodies from cancer patients (22, 23)
  • 2004: Validation of GRP78 as a target in prostate and breast cancer (24)
  • 2008: Horizontal follow-up of humoral response in patients (25)
  • 2009: Functional definition of human CLL based on fingerprinting BCR (26)


Obesity Reversal through Vascular Targeting

  • 2004: Targeted treatment in preclinical models of obesity (27)
  • 2007: GMP grade peptidomimetic drug custom-ordered and received
  • 2009: Activity and toxicity study in obese baboons and Rhesus monkeys (28)
  • 2009: Direct selection of ligands to human white adipose tissue in cancer patients (6)
  • 2010: IND filed for a Phase I clinical trial in obese prostate cancer patients (NCT01262664)
  • 2011: Response to Clinical Hold filed with the FDA
  • 2012: Clinical Hold removed, “safe to proceed” granted, Phase I trial active as of May 2012 (Protocol No. 2010-0369)
  • 2013: Patient accrual at MD Anderson Cancer Center in parallel with a lead optimization program
  • 2014: Mechanistic studies of weight loss mediated by adipotide


Hybridoma and hybridoma-free Generation and Production of Antibodies

  • 2003: Technology design and development
  • 2004: Hybridoma-free monoclonals: concept and reduction to practice (29)


Recombinant Antibody Phage Display Library and in vivo screening

  • 2014: Application of renewable human recombinant antibodies pipeline recognizing cancer biomarkers (30)



  1. Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do KA, Logothetis CJ, Pasqualini R. 2002. Nat Med 8: 121-7
  2. Zurita AJ, Troncoso P, Cardo-Vila M, Logothetis CJ, Pasqualini R, Arap W. 2004. Cancer Res 64: 435-9
  3. Pentz RD, Cohen CB, Wicclair M, DeVita MA, Flamm AL, Youngner SJ, Hamric AB, McCabe MS, Glover JJ, Kittiko WJ, Kinlaw K, Keller J, Asch A, Kavanagh JJ, Arap W. 2005. Nature Medicine 11: 1145-49
  4. Pentz RD, Flamm AL, Pasqualini R, Logothetis CJ, Arap W. 2003. Hastings Cent Rep 33: 20-6
  5. Kolonin MG, Sun J, Do KA, Vidal CI, Ji Y, Baggerly KA, Pasqualini R, Arap W. 2006. FASEB J 20: 979-81
  6. Staquicini FI, Cardo-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN, Sergeeva A, Efstathiou E, Sun J, Almeida NF, Tu SM, Botz GH, Wallace MJ, O'Connell DJ, Krajewski S, Gershenwald JE, Molldrem JJ, Flamm AL, Koivunen E, Pentz RD, Dias-Neto E, Setubal JC, Cahill DJ, Troncoso P, Do KA, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. 2011. Proc Natl Acad Sci U S A 108: 18637-42
  7. Pasqualini R, Millikan RE, Christianson DR, Cardo-Vila M, Driessen WH, Giordano RJ, Hajitou A, Hoang AG, Wen S, Barnhart KF, Baze WB, Marcott VD, Hawke DH, Do KA, Navone NM, Efstathiou E, Troncoso P, Lobb RR, Logothetis CJ, Arap W. 2015. Cancer 121: 2411-21
  8. Karjalainen K, Jaalouk DE, Bueso-Ramos C, Bover L, Sun Y, Kuniyasu A, Driessen WH, Cardo-Vila M, Rietz C, Zurita AJ, O'Brien S, Kantarjian HM, Cortes JE, Calin GA, Koivunen E, Arap W, Pasqualini R. 2015. Clin Cancer Res 21: 3041-51
  9. Sidman RL, Li J, Lawrence M, Hu W, Musso GF, Giordano RJ, Cardo-Vila M, Pasqualini R, Arap W. 2015. Sci Transl Med 7: 309ra165
  10. Arap W, Pasqualini R, Rajotte D, Ruoslahti E. 2000. A Laboratory Manual. In vivo Phage Display. Cold Spring Harbor: Cold Spring Harbor Laboratory Press
  11. Arap W, Pasqualini R, Ruoslahti E. 1998. Science 279: 377-80
  12. Muller OJ, Kaul F, Weitzman MD, Pasqualini R, Arap W, Kleinschmidt JA, Trepel M. 2003. Nat Biotechnol 21: 1040-6
  13. Souza GR, Christianson DR, Staquicini FI, Ozawa MG, Snyder EY, Sidman RL, Miller JH, Arap W, Pasqualini R. 2006. Proc Natl Acad Sci U S A 103: 1215-20
  14. Souza GR, Levin CS, Hajitou A, Pasqualini R, Arap W, Miller JH. 2006. Anal Chem 78: 6232-7
  15. Hajitou A, Rangel R, Trepel M, Soghomonyan S, Gelovani JG, Alauddin MM, Pasqualini R, Arap W. 2007. Nat Protoc 2: 523-31
  16. Hajitou A, Trepel M, Lilley CE, Soghomonyan S, Alauddin MM, Marini FC, 3rd, Restel BH, Ozawa MG, Moya CA, Rangel R, Sun Y, Zaoui K, Schmidt M, von Kalle C, Weitzman MD, Gelovani JG, Pasqualini R, Arap W. 2006. Cell 125: 385-98
  17. Hajitou A, Lev DC, Hannay JA, Korchin B, Staquicini FI, Soghomonyan S, Alauddin MM, Benjamin RS, Pollock RE, Gelovani JG, Pasqualini R, Arap W. 2008. Proc Natl Acad Sci U S A 105: 4471-6
  18. Paoloni MC, Tandle A, Mazcko C, Hanna E, Kachala S, Leblanc A, Newman S, Vail D, Henry C, Thamm D, Sorenmo K, Hajitou A, Pasqualini R, Arap W, Khanna C, Libutti SK. 2009. PLoS One 4: e4972
  19. Yuan Z, Syrkin G, Adem A, Geha R, Pastoriza J, Vrikshajanani C, Smith T, Quinn TJ, Alemu G, Cho H, Barrett CJ, Arap W, Pasqualini R, Libutti SK. 2013. Cancer Gene Ther 20: 46-56
  20. Staquicini FI, Ozawa MG, Moya CA, Driessen WH, Barbu EM, Nishimori H, Soghomonyan S, Flores LG, 2nd, Liang X, Paolillo V, Alauddin MM, Basilion JP, Furnari FB, Bogler O, Lang FF, Aldape KD, Fuller GN, Hook M, Gelovani JG, Sidman RL, Cavenee WK, Pasqualini R, Arap W. 2011. J Clin Invest 121: 161-73
  21. Salameh A, Lee AK, Cardo-Vila M, Nunes DN, Efstathiou E, Staquicini FI, Dobroff AS, Marchio S, Navone NM, Hosoya H, Lauer RC, Wen SJ, Salmeron CC, Hoang A, Newsham I, Lima LA, Carraro DM, Oliviero S, Kolonin MG, Sidman RL, Do KA, Troncoso P, Logothetis CJ, Brentani RR, Calin GA, Cavenee WK, Dias-Neto E, Pasqualini R, Arap W. 2015. Proceedings of the National Academy of Sciences of the United States of America 112: 8403-8
  22. Mintz PJ, Kim J, Do KA, Wang X, Zinner RG, Cristofanilli M, Arap MA, Hong WK, Troncoso P, Logothetis CJ, Pasqualini R, Arap W. 2003. Nat Biotechnol 21: 57-63
  23. Vidal CI, Mintz PJ, Lu K, Ellis LM, Manenti L, Giavazzi R, Gershenson DM, Broaddus R, Liu J, Arap W, Pasqualini R. 2004. Oncogene 23: 8859-67
  24. Arap MA, Lahdenranta J, Mintz PJ, Hajitou A, Sarkis AS, Arap W, Pasqualini R. 2004. Cancer Cell 6: 275-84
  25. Mintz PJ, Rietz AC, Cardo-Vila M, Ozawa MG, Dondossola E, Do KA, Kim J, Troncoso P, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. 2015. Proc Natl Acad Sci U S A 112: 2515-20
  26. Binder M, Muller F, Jackst A, Lechenne B, Pantic M, Bacher U, Zu Eulenburg C, Veelken H, Mertelsmann R, Pasqualini R, Arap W, Trepel M. 2011. Cancer 117: 1891-900
  27. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. 2004. Nat Med 10: 625-32
  28. Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. 2011. Sci Transl Med 3: 108-12
  29. Pasqualini R, Arap W. 2004. Proc Natl Acad Sci U S A 101: 257-9
  30. Ferrara F, D'Angelo S, Gaiotto T, Naranjo L, Tian H, Graslund S, Dobrovetsky E, Hraber P, Lund-Johansen F, Saragozza S, Sblattero D, Kiss C, Bradbury AR. 2015. MAbs 7: 32-41