Skip to main content

Advertisement

SpringerLink
Log in

Optimising the Delivery of Tubulin Targeting Agents through Antibody Conjugation

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Despite their side effect profile, there currently remains a heavy reliance on traditional cytotoxics and particularly tubulin targeting agents in cancer chemotherapy. To address this concern, significant progress has been made in the selective delivery of drugs to the tumour site. This review will examine the published data in support of the hypothesis that forming antibody conjugates of tubulin targeting agents is an effective approach towards their more effective delivery to the tumour site. Particular emphasis will be placed on the diversity of concepts under investigation, the efficacy of resultant conjugates, evidence of decreased resistance and the side effect profiles of the conjugates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

ADC:

antibody-drug conjugate

ALCL:

anaplastic large cell lymphoma

BMPEO:

bis-maleimido-trioxyethylene glycol

DM:

drug maytansinoid

EGFR:

epidermal growth factor receptor

HER2:

human epidermal growth factor receptor 2

IgG:

immunoglobulin G

mAb:

monoclonal antibody

MC:

maleimidocaproyl

MDR-1:

multidrug resistance protein-1

MMAE:

monomethyl auristatin E

MMAF:

monomethyl auristatin F

MTD:

maximum tolerated dose

PAB:

p-aminobenzyloxy carbonyl

PABC:

p-aminobenzyl carbonyl

PEG:

polyethylene glycol

PSMA:

prostate specific membrane antigen

Siglec:

sialic acid binding Ig-like lectins

SMCC:

succinimidyl trans-4-(maleimidylmethyl) cyclohexane-1-carboxylate

SPDB:

N-succinimidyl-3-(2-pyridylthio) propionate

SPP:

N-succinimidyl 4-(2-pyridyldithio) pentanoate

vc:

valine-citrulline

References

  1. Chari RV. Targeted delivery of chemotherapeutics: tumor-activated prodrug therapy. Adv Drug Deliv Rev. 1998;31(1–2):89–104.

    Article  PubMed  CAS  Google Scholar 

  2. Kavallaris M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer. 2010;10(3):194–204.

    Article  PubMed  CAS  Google Scholar 

  3. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4(4):253–65.

    Article  PubMed  CAS  Google Scholar 

  4. Dumontet C, Jordan MA. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov. 2010;9(10):790–803.

    Article  PubMed  CAS  Google Scholar 

  5. Kavallaris M, Verrills NM, Hill BT. Anticancer therapy with novel tubulin-interacting drugs. Drug Resist Updat. 2001;4(6):392–401.

    Article  PubMed  CAS  Google Scholar 

  6. Lambert JM. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol. 2005;5(5):543–9.

    Article  PubMed  CAS  Google Scholar 

  7. Vlahov IR, Wang Y, Kleindl PJ, Leamon CP. Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part II: Folic acid conjugates of tubulysins and their hydrazides. Bioorg Med Chem Lett. 2008;18(16):4558–61.

    Article  PubMed  CAS  Google Scholar 

  8. Kupchan SM, Komoda Y, Court WA, Thomas GJ, Smith RM, Karim A, et al. Tumor inhibitors. LXXIII. Maytansine, a novel antileukemic ansa macrolide from Maytenus ovatus. J Am Chem Soc. 1972;94(4):1354–6.

    Article  PubMed  CAS  Google Scholar 

  9. Oroudjev E, Lopus M, Wilson L, Audette C, Provenzano C, Erickson H, et al. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability. Mol Cancer Ther. 2010;9(10):2700–13.

    Article  PubMed  CAS  Google Scholar 

  10. Lopus M. Antibody-DM1 conjugates as cancer therapeutics. Cancer Lett. 2011;307(2):113–8.

    Article  PubMed  CAS  Google Scholar 

  11. Chari RVJ, Martell BA, Gross JL, Cook SB, Shah SA, Blättler WA, et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res. 1992;52(1):127–31.

    PubMed  CAS  Google Scholar 

  12. Lambert JM. Antibody-maytansinoid conjugates as anticancer therapeutics: Proving their benefit. Hum Antibodies. 2007;16(1–2):5–8.

    Google Scholar 

  13. Yusuf RZ, Duan Z, Lamendola DE, Penson RT, Seiden MV. Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets. 2003;3(1):1–19.

    Article  PubMed  CAS  Google Scholar 

  14. Argiris A, Duffy AG, Kummar S, Simone NL, Arai Y, Kim SW, et al. Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer. Clin Cancer Res. 2011;17(17):5755–64.

    Article  PubMed  CAS  Google Scholar 

  15. Kim KM, McDonagh CF, Westendorf L, Brown LL, Sussman D, Feist T, et al. Anti-CD30 diabody-drug conjugates with potent antitumor activity. Mol Cancer Ther. 2008;7(8):2486–97.

    Article  PubMed  CAS  Google Scholar 

  16. Guillemard V, Uri Saragovi H. Prodrug chemotherapeutics bypass p-glycoprotein resistance and kill tumors in vivo with high efficacy and target-dependent selectivity. Oncogene. 2004;23(20):3613–21.

    Article  PubMed  CAS  Google Scholar 

  17. Teicher BA, Chari RVJ. Antibody conjugate therapeutics: challenges and potential. Clin Cancer Res. 2011;17(20):6389–97.

    Article  PubMed  CAS  Google Scholar 

  18. Christiansen J, Rajasekaran AK. Biological impediments to monoclonal antibody-based cancer immunotherapy. Mol Cancer Ther. 2004;3(11):1493–501.

    PubMed  CAS  Google Scholar 

  19. Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102(4):1458–65.

    Article  PubMed  CAS  Google Scholar 

  20. Ducry L, Stump B. Antibody−drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2009;21(1):5–13.

    Article  Google Scholar 

  21. Webb S. Pharma interest surges in antibody drug conjugates. Nat Biotechnol. 2011;29(4):297–8.

    Article  PubMed  CAS  Google Scholar 

  22. Goldenberg DM. Monoclonal antibodies in cancer detection and therapy. Am J Med. 1993;94(3):297–312.

    Article  PubMed  CAS  Google Scholar 

  23. Wu X, Ojima I. Tumor specific novel taxoid-monoclonal antibody conjugates. Curr Med Chem. 2004;11(4):429–38.

    Article  PubMed  CAS  Google Scholar 

  24. Widdison WC, Wilhelm SD, Cavanagh EE, Whiteman KR, Leece BA, Kovtun Y, et al. Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem. 2006;49(14):4392–408.

    Article  PubMed  CAS  Google Scholar 

  25. Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res. 2004;10(20):7063–70.

    Article  PubMed  CAS  Google Scholar 

  26. Tijink BM, Buter J, de Bree R, Giaccone G, Lang MS, Staab A, et al. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006;12(20 Pt 1):6064–72.

    Article  PubMed  CAS  Google Scholar 

  27. Garanger E, Boturyn D, Dumy P. Tumor targeting with RGD peptide ligands-design of new molecular conjugates for imaging and therapy of cancers. Anticancer Agents Med Chem. 2007;7(5):552–8.

    PubMed  CAS  Google Scholar 

  28. Yokota T, Milenic DE, Whitlow M, Schlom J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992;52(12):3402–8.

    PubMed  CAS  Google Scholar 

  29. Adams GP, Schier R, Marshall K, Wolf EJ, McCall AM, Marks JD, et al. Increased affinity leads to improved selective tumor delivery of single-chain Fv antibodies. Cancer Res. 1998;58(3):485–90.

    PubMed  CAS  Google Scholar 

  30. Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, et al. Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2–positive breast cancer. Clin Cancer Res. 2010;16(19):4769–78.

    Article  PubMed  CAS  Google Scholar 

  31. Braun S, Schlimok G, Heumos I, Schaller G, Riethdorf L, Riethmuller G, et al. ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients. Cancer Res. 2001;61(5):1890–5.

    PubMed  CAS  Google Scholar 

  32. Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD, Weir S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotech. 2008;26(8):925–32.

    Article  CAS  Google Scholar 

  33. Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov. 2006;5(2):147–59.

    Article  PubMed  CAS  Google Scholar 

  34. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006;66(8):4426–33.

    Article  PubMed  CAS  Google Scholar 

  35. Lopus M, Oroudjev E, Wilson L, Wilhelm S, Widdison W, Chari R, et al. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules. Mol Cancer Ther. 2010;9(10):2689–99.

    Article  PubMed  CAS  Google Scholar 

  36. Kovtun YV, Audette CA, Ye Y, Xie H, Ruberti MF, Phinney SJ, et al. Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res. 2006;66(6):3214–21.

    Article  PubMed  CAS  Google Scholar 

  37. Kovtun YV, Goldmacher VS. Cell killing by antibody–drug conjugates. Cancer Lett. 2007;255(2):232–40.

    Article  PubMed  CAS  Google Scholar 

  38. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, et al. The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009;15(12):4028–37.

    Article  PubMed  CAS  Google Scholar 

  39. Lutz RJ, Whiteman KR. Antibody-maytansinoid conjugates for the treatment of myeloma. Mabs. 2009;1(6):548–51.

    Article  PubMed  Google Scholar 

  40. Beck A, Senter P, Chari R. World antibody drug conjugate Summit Europe: February 21-23, 2011; Frankfurt, Germany. Mabs. 2011;3(4):331–7.

    Article  PubMed  Google Scholar 

  41. Polson AG, Calemine-Fenaux J, Chan P, Chang W, Christensen E, Clark S, et al. Antibody-drug conjugates for the treatment of non-Hodgkin’s lymphoma: target and linker-drug selection. Cancer Res. 2009;69(6):2358–64.

    Article  PubMed  CAS  Google Scholar 

  42. Ma DS, Hopf CE, Malewicz AD, Donovan GP, Senter PD, Goeckeler WF, et al. Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specific membrane antigen. Clin Cancer Res. 2006;12(8):2591–6.

    Article  PubMed  CAS  Google Scholar 

  43. Podgorski I, Sloane BF. Cathepsin B and its role(s) in cancer progression. Biochem Soc Symp. 2003;70:263–76.

    PubMed  CAS  Google Scholar 

  44. Doronina SO, Toki BE, Torgov MY, Mendelsohn BA, Cerveny CG, Chace DF, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol. 2003;21(7):778.

    Article  PubMed  CAS  Google Scholar 

  45. Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res. 2002;62(13):3736–42.

    PubMed  CAS  Google Scholar 

  46. Doronina SO, Mendelsohn BA, Bovee TD, Cerveny CG, Alley SC, Meyer DL, et al. Enhanced activity of monomethylauristatin f through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2005;17(1):114–24.

    Article  Google Scholar 

  47. Kovtun YV, Audette CA, Mayo MF, Jones GE, Doherty H, Maloney EK, et al. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res. 2010;70(6):2528–37.

    Article  PubMed  CAS  Google Scholar 

  48. Zhao RY, Wilhelm SD, Audette C, Jones G, Leece BA, Lazar AC, et al. Synthesis and evaluation of hydrophilic linkers for antibody–maytansinoid conjugates. J Med Chem. 2011;54(10):3606–23.

    Article  PubMed  CAS  Google Scholar 

  49. Jeffrey SC, Andreyka JB, Bernhardt SX, Kissler KM, Kline T, Lenox JS, et al. Development and properties of β-glucuronide linkers for monoclonal antibody−drug conjugates. Bioconjug Chem. 2006;17(3):831–40.

    Article  PubMed  CAS  Google Scholar 

  50. Albin N, Massaad L, Toussaint C, Mathieu MC, Morizet J, Parise O, et al. Main drug-metabolizing enzyme systems in human breast tumors and peritumoral tissues. Cancer Res. 1993;53(15):3541–6.

    PubMed  CAS  Google Scholar 

  51. Gilbert CW, McGowan EB, Seery GB, Black KS, Pegram MD. Targeted prodrug treatment of HER-2-positive breast tumor cells using trastuzumab and paclitaxel linked by A-Z-CINN™ Linker. J Exp Ther Oncol. 2003;3(1):27–35.

    Article  PubMed  CAS  Google Scholar 

  52. Ojima I, Geng X, Wu X, Qu C, Borella CP, Xie H, et al. Tumor-specific novel taxoid-monoclonal antibody conjugates. J Med Chem. 2002;45(26):5620–3.

    Article  PubMed  CAS  Google Scholar 

  53. Polson AG, Williams M, Gray AM, Fuji RN, Poon KA, McBride J, et al. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin’s lymphoma. Leukemia. 2010;24(9):1566–73.

    Article  PubMed  CAS  Google Scholar 

  54. Law CL, Cerveny CG, Gordon KA, Klussman K, Mixan BJ, Chace DF, et al. Efficient elimination of B-lineage lymphomas by anti-CD20-auristatin conjugates. Clin Cancer Res. 2004;10(23):7842–51.

    Article  PubMed  CAS  Google Scholar 

  55. Yazawa N, Hamaguchi Y, Poe JC, Tedder TF. Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease. Proc Natl Acad Sci USA. 2005;102(42):15178–83.

    Article  PubMed  CAS  Google Scholar 

  56. Gerber HP, Kung-Sutherland M, Stone I, Morris-Tilden C, Miyamoto J, McCormick R, et al. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Blood. 2009;113(18):4352–61.

    Article  PubMed  CAS  Google Scholar 

  57. Polson AG, Yu SF, Elkins K, Zheng B, Clark S, Ingle GS, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110(2):616–23.

    Article  PubMed  CAS  Google Scholar 

  58. Dornan D, Bennett F, Chen Y, Dennis M, Eaton D, Elkins K, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721–9.

    Article  PubMed  CAS  Google Scholar 

  59. Zheng B, Fuji RN, Elkins K, Yu S-F, Fuh FK, Chuh J, et al. In vivo effects of targeting CD79b with antibodies and antibody-drug conjugates. Mol Cancer Ther. 2009;8(10):2937–46.

    Article  PubMed  CAS  Google Scholar 

  60. Ab O, Bartle LM, Rui L, Coccia J, Johnson HA, Whiteman KR, et al. Abstract 4576: IMGN853, an anti-Folate Receptor I antibody-maytansinoid conjugate for targeted cancer therapy. Cancer Res. 2011;71(8 Supplement):4576.

    Article  Google Scholar 

  61. Katz J, Janik JE, Younes A. Brentuximab vedotin (SGN-35). Clin Cancer Res. 2011;17(20):6428–36.

    Article  PubMed  CAS  Google Scholar 

  62. Liu C, Tadayoni BM, Bourret LA, Mattocks KM, Derr SM, Widdison WC, et al. Eradication of large colon tumor xenografts by targeted delivery of maytansinoids. Proc Natl Acad Sci USA. 1996;93(16):8618–23.

    Article  PubMed  CAS  Google Scholar 

  63. Tolcher AW, Ochoa L, Hammond LA, Patnaik A, Edwards T, Takimoto C, et al. Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg Antigen: a Phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol. 2003;21(2):211–22.

    Article  PubMed  CAS  Google Scholar 

  64. Robak T, Robak P, Smolewski P. TRU-016, a humanized anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies. Curr Opin Investig Drugs. 2009;10(12):1383–90.

    PubMed  CAS  Google Scholar 

  65. Park PU, Yi Y, Li M, Chicklas S, Lai KC, Mayo MF, et al. Abstract 2830: antibody and linker selection for the anti-CD37 antibody-maytansinoid conjugate IMGN529 for the treatment of B-cell malignancies. Cancer Res. 2011;71(8 Supplement):2830.

    Article  Google Scholar 

  66. Ireton RC, Chen J. EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics. Curr Cancer Drug Targets. 2005;5(3):149–57.

    Article  PubMed  CAS  Google Scholar 

  67. Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB. The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene. 2000;19(52):6043.

    Article  PubMed  CAS  Google Scholar 

  68. Lee J-W, Stone RL, Lee SJ, Nam EJ, Roh J-W, Nick AM, et al. EphA2 targeted chemotherapy using an antibody drug conjugate in endometrial carcinoma. Clin Cancer Res. 2010;16(9):2562–70.

    Article  PubMed  CAS  Google Scholar 

  69. Junttila T, Li G, Parsons K, Phillips G, Sliwkowski M. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128(2):347–56.

    Article  PubMed  CAS  Google Scholar 

  70. Mathew J, Perez EA. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive breast cancer: a review. Curr Opin Oncol. 2011;23(6):594–600.

    Article  PubMed  CAS  Google Scholar 

  71. Younes A, Yasothan U, Kirkpatrick P. Brentuximab vedotin. Nat Rev Drug Discov. 2012;11(1):19–20.

    Article  PubMed  CAS  Google Scholar 

  72. Oflazoglu E, Kissler KM, Sievers EL, Grewal IS, Gerber H-P. Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma. Br J Haematol. 2008;142(1):69–73.

    Article  PubMed  CAS  Google Scholar 

  73. Blanc V, Bousseau A, Caron A, Carrez C, Lutz RJ, Lambert JM. SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res. 2011;17(20):6448–58.

    Article  PubMed  CAS  Google Scholar 

  74. Sanofi-Aventis. An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 12 May 02]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01472887?term=SAR3419&rank=1 NLM Identifier: NCT01472887].

  75. MedImmune LLC. Study of MEDI-547 to Evaluate the Safety, Tolerability, and Biologic Activity of IV Administration in Subjects With Relapsed or Refractory Solid Tumors. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 12 Feb 23]. Available from: http://clinicaltrials.gov/ct2/show/NCT00796055?intr=%22MEDI-547%22&rank=1 NLM Identifier: NCT00796055.

  76. Oflazoglu E, Stone IJ, Gordon K, Wood CG, Repasky EA, Grewal IS, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor Auristatin via an uncleavable linker. Clin Cancer Res. 2008;14(19):6171–80.

    Article  PubMed  CAS  Google Scholar 

  77. Ricart AD. Immunoconjugates against solid tumors: mind the gap. Clin Pharmacol Ther. 2011;89(4):513–23.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments and Disclosures

The authors would like to acknowledge funding from the Irish Council for Science Engineering and Technology (IRCSET) and Enterprise Ireland.

Author information

Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland

    Gary D. Stack & John J. Walsh

Authors
  1. Gary D. Stack
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John J. Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John J. Walsh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stack, G.D., Walsh, J.J. Optimising the Delivery of Tubulin Targeting Agents through Antibody Conjugation. Pharm Res 29, 2972–2984 (2012). https://doi.org/10.1007/s11095-012-0810-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-012-0810-9

Key Words

Search

Navigation