Arap/Pasqualini Laboratory – Timelines and Milestones 04/04/2017


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)
  • 2016: Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors (10)
  • 2016: Expression of interleukin-11 receptor in lung clinical samples led to studies             showing BMTP-11 activity in pre-clinical models (11)
  • 2017: Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone (12)
  • 2017: Therapeutic application of BMTP-11 in models of human osteosarcoma (13)


Ligand-directed Targeting, Nanotechnology & Molecular-genetic Imaging

  • 1998-2000: Tumor targeting in preclinical models (14, 15)
  • 2003: Display of combinatorial peptide libraries on AAV particles (16)
  • 2005: Self-assembled biocompatible Au-phage network (17, 18)
  • 2006: AAV-phage (AAVP) for molecular imaging (19, 20)
  • 2008: AAVP predicts drug response in sarcoma: towards an imaging transcriptome (21)
  • 2009: Phase I-II trial of targeted TNF in pet dogs with spontaneous cancer (22)
  • 2010: Integration of the AAVP vector system with other anti-cancer therapies shows synergistic anti-tumor activity (23)
  • 2011: Iron-mimicking peptide in AAVP crosses blood-brain barrier to image and treat glioblastoma (24)
  • 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 (25)
  • 2016: An integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release (Hosoya et al. 2016)
  • 2016: AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas (26)
  • 2016: Ligand-targeted theranostic nanomedicines against cancer (27)
  • 2016: Optimizing in vivo selection kinetics of AAVP library screening to optimize transgene targeting to the brain (28).
  • 2016: In vivo delivery of Herpes Simplex Virus thymidine kinase (HSVtk) gene by             GRP78-targeted AAVP to mice bearing human SUM190 orthotopic inflammatory            breast cancer tumors for simultaneous diagnosis by PET imaging and tumor                   treatment (29)
  • 2016: In vivo delivery and treatment of a patient-derived aggressive variant prostate cancer, MDA-PCa-11b, by SNTRVAP-AAVP containing the HSVtk transgene             (30)
  • 2017: An AAVP-based solid-phase transducing matrix for transgene delivery: potential for translational applications (31)
  • 2017: Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting (32)


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 (33, 34)
  • 2004: Validation of GRP78 as a target in prostate and breast cancer (35)
  • 2008: Horizontal follow-up of humoral response in patients (36)
  • 2009: Functional definition of human CLL based on fingerprinting BCR (37)


Obesity Reversal through Vascular Targeting

  • 2004: Targeted treatment in preclinical models of obesity (38)
  • 2007: GMP grade peptidomimetic drug custom-ordered and received
  • 2009: Activity and toxicity study in obese baboons and Rhesus monkeys (39)
  • 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
  • 2016: Interaction of prohibitin with annexin 2 regulates fatty acid transport between the endothelium and adipocytes via the CD36 fatty acid transporter (40)


Hybridoma and hybridoma-free Generation and Production of Antibodies

  • 2003: Technology design and development
  • 2004: Hybridoma-free monoclonals: concept and reduction to practice (41)


Recombinant Antibody Phage Display Library and in vivo screening

  • 2014: Application of renewable human recombinant antibodies pipeline recognizing cancer biomarkers (42)



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  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
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  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. Dondossola E, Dobroff AS, Marchio S, Cardo-Vila M, Hosoya H, Libutti SK, Corti A, Sidman RL, Arap W, Pasqualini R. 2016. Proc Natl Acad Sci U S A 113: 2223-8
  11. Cardo-Vila M, Marchio S, Sato M, Staquicini FI, Smith TL, Bronk JK, Yin G, Zurita AJ, Sun M, Behrens C, Sidman RL, Lee JJ, Hong WK, Wistuba, II, Arap W, Pasqualini R. 2016. Am J Pathol 186: 2162-70
  12. Kolonin MG, Sergeeva A, Staquicini DI, Smith TL, Tarleton CA, Molldrem JJ, Sidman RL, Marchio S, Pasqualini R, Arap W. 2017. Cancer Res 77: 3144-50
  13. Lewis VO, Devarajan E, Cardo-Vila M, Thomas DG, Kleinerman ES, Marchio S, Sidman RL, Pasqualini R, Arap W. 2017. Proc Natl Acad Sci U S A 114: 8065-70
  14. Arap W, Pasqualini R, Rajotte D, Ruoslahti E. 2000. A Laboratory Manual. In vivo Phage Display. Cold Spring Harbor: Cold Spring Harbor Laboratory Press
  15. Arap W, Pasqualini R, Ruoslahti E. 1998. Science 279: 377-80
  16. Muller OJ, Kaul F, Weitzman MD, Pasqualini R, Arap W, Kleinschmidt JA, Trepel M. 2003. Nat Biotechnol 21: 1040-6
  17. 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
  18. Souza GR, Levin CS, Hajitou A, Pasqualini R, Arap W, Miller JH. 2006. Anal Chem 78: 6232-7
  19. Hajitou A, Rangel R, Trepel M, Soghomonyan S, Gelovani JG, Alauddin MM, Pasqualini R, Arap W. 2007. Nat Protoc 2: 523-31
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. Salameh A, Lee AK, Cardo-Vila M, Nunes DN, Efstathiou E, Staquicini FI, Dobroff AS, Marchio S, Navone NM, Hosoya H, Lauer RC, Wen S, 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. Proc Natl Acad Sci U S A 112: 8403-8
  26. Smith TL, Yuan Z, Cardo-Vila M, Sanchez Claros C, Adem A, Cui MH, Branch CA, Gelovani JG, Libutti SK, Sidman RL, Pasqualini R, Arap W. 2016. Proc Natl Acad Sci U S A 113: 2466-71
  27. Yao VJ, D'Angelo S, Butler KS, Theron C, Smith TL, Marchio S, Gelovani JG, Sidman RL, Dobroff AS, Brinker CJ, Bradbury AR, Arap W, Pasqualini R. 2016. J Control Release 240: 267-86
  28. Korbelin J, Sieber T, Michelfelder S, Lunding L, Spies E, Hunger A, Alawi M, Rapti K, Indenbirken D, Muller OJ, Pasqualini R, Arap W, Kleinschmidt JA, Trepel M. 2016. Mol Ther 24: 1050-61
  29. Dobroff AS, D'Angelo S, Eckhardt BL, Ferrara F, Staquicini DI, Cardo-Vila M, Staquicini FI, Nunes DN, Kim K, Driessen WH, Hajitou A, Lomo LC, Barry M, Krishnamurthy S, Sahin A, Woodward WA, Prossnitz ER, Anderson RL, Dias-Neto E, Brown-Glaberman UA, Royce ME, Ueno NT, Cristofanilli M, Hortobagyi GN, Marchio S, Gelovani JG, Sidman RL, Arap W, Pasqualini R. 2016. Proc Natl Acad Sci U S A
  30. Ferrara F, Staquicini DI, Driessen WH, D'Angelo S, Dobroff AS, Barry M, Lomo LC, Staquicini FI, Cardo-Vila M, Soghomonyan S, Alauddin MM, Flores LG, 2nd, Arap MA, Lauer RC, Mathew P, Efstathiou E, Aparicio AM, Troncoso P, Navone NM, Logothetis CJ, Marchio S, Gelovani JG, Sidman RL, Pasqualini R, Arap W. 2016. Proc Natl Acad Sci U S A
  31. Smith TL, Souza GR, Sidman RL, Arap W, Pasqualini R. 2017. Cancer Gene Ther
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  33. 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
  34. 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
  35. Arap MA, Lahdenranta J, Mintz PJ, Hajitou A, Sarkis AS, Arap W, Pasqualini R. 2004. Cancer Cell 6: 275-84
  36. 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
  37. 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
  38. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. 2004. Nat Med 10: 625-32
  39. 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: 108ra12
  40. Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. 2016. JCI Insight 1
  41. Pasqualini R, Arap W. 2004. Proc Natl Acad Sci U S A 101: 257-9
  42. 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