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Translational Therapeutics

Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer

British Journal of Cancer volume 133, pages 1218–1228 (2025)Cite this article

Subjects

Abstract

Background

Antibody-drug conjugates (ADCs) are a significant advancement in targeted cancer therapy, but none are approved for colorectal cancer (CRC). LGR4/5/6, highly expressed in most CRCs, are promising targets. While LGR5-targeting ADCs show strong anti-tumor effects, their efficacy is limited by LGR5 loss in some CRC cells. RSPO4, a natural ligand for LGR4/5/6, binds all three receptors with high affinity. This research develops RSPO4-based peptibody drug-conjugates (PDCs) to simultaneously target LGR4/5/6, offering a novel therapeutic approach for CRC.

Methods

LGR4/5/6 expression in CRCs was analysed using RNA-seq datasets and Western blot. Peptibody binding affinities were measured, conjugated to camptothecin analog, CPT2, and tested for cytotoxicity in CRC cell lines. Antitumor efficacy was evaluated in vivo using CRC cell line and patient-derived xenograft (PDX) models.

Results

Peptibody was engineered by fusing a mutant RSPO4 furin-domain to human IgG1 Fc, retaining high-affinity LGR4/5/6 binding without enhancing Wnt/β-catenin signalling. Conjugated with CPT2 molecules, the PDC showed strong antitumor activity in CRC cell lines and dose-dependent tumor growth inhibition in xenograft and patient-derived models.

Conclusion

Preclinical data showed that LGR4/5/6-targeting PDC exhibited potent cytotoxicity in vitro and robust antitumor efficacy in CRC xenograft and PDX models, making its potential as a promising therapeutic approach for CRC.

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Fig. 1: Design and characterisation of peptibodies R462 and R465.
Fig. 2: Design, conjugation and characterisation of PDCs R462-CPT2 and R465-CPT2.
Fig. 3: Expression profile of LGR4/5 and In vitro cytotoxicity of R462-CPT2 and R465-CPT2 in six CRC cell lines.
Fig. 4: Anti-tumor potency of R462-CPT2 in xenograft model of LoVo cells.
Fig. 5: Anti-tumor effect of R462-CPT2 in three PDX models of CRC.
Fig. 6: Mouse toxicity study results.

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Data availability

All the relevant data generated in this manuscript that support the findings of this study are available upon request from the authors.

References

  1. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394:1467–80. https://doi.org/10.1016/S0140-6736(19)32319-0.

    Article  PubMed  Google Scholar 

  2. Morris VK, Kennedy EB, Baxter NN, Benson AB 3rd, Cercek A, Cho M, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2023;41:678–700. https://doi.org/10.1200/JCO.22.01690.

    Article  PubMed  Google Scholar 

  3. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10:789–99. https://doi.org/10.1038/nm1087nm1087.

    Article  CAS  PubMed  Google Scholar 

  4. de Lau W, Barker N, Clevers H. WNT signaling in the normal intestine and colorectal cancer. Front Biosci. 2007;12:471–91.

    Article  PubMed  Google Scholar 

  5. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA. 2011;108:11452–7. https://doi.org/10.1073/pnas.1106083108.

    Article  PubMed  PubMed Central  Google Scholar 

  6. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 2011;476:293–7. https://doi.org/10.1038/nature10337.

    Article  CAS  PubMed  Google Scholar 

  7. Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, et al. Recurrent R-spondin fusions in colon cancer. Nature. 2012;488:660–4. https://doi.org/10.1038/nature11282.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. de Lau WB, Snel B, Clevers HC. The R-spondin protein family. Genome Biol. 2012;13:242 https://doi.org/10.1186/gb-2012-13-3-242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nam JS, Park E, Turcotte TJ, Palencia S, Zhan X, Lee J, et al. Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Dev Biol. 2007;311:124–35. https://doi.org/10.1016/j.ydbio.2007.08.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X. R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J Biol Chem. 2007;282:15903–11. https://doi.org/10.1074/jbc.M701927200.

    Article  CAS  PubMed  Google Scholar 

  11. Park S, Cui J, Yu W, Wu L, Carmon KS, Liu QJ. Differential activities and mechanisms of the four R-spondins in potentiating Wnt/beta-catenin signaling. J Biol Chem. 2018;293:9759–69. https://doi.org/10.1074/jbc.RA118.002743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dubey R, van Kerkhof P, Jordens I, Malinauskas T, Pusapati GV, McKenna JK, et al. R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling. eLife. 2020; 9. https://doi.org/10.7554/eLife.54469.

  13. Chen PH, Chen X, Lin Z, Fang D, He X. The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev. 2013;27:1345–50. https://doi.org/10.1101/gad.219915.113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zebisch M, Jones EY. Crystal structure of R-spondin 2 in complex with the ectodomains of its receptors LGR5 and ZNRF3. J Struct Biol. 2015;191:149–55. https://doi.org/10.1016/j.jsb.2015.05.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, et al. Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5. Cell Rep. 2013;3:1885–92. https://doi.org/10.1016/j.celrep.2013.06.009.

    Article  CAS  PubMed  Google Scholar 

  16. Xu K, Xu Y, Rajashankar KR, Robev D, Nikolov DB. Crystal structures of Lgr4 and its complex with R-spondin1. Structure. 2013;21:1683–9. https://doi.org/10.1016/j.str.2013.07.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485:195–200. https://doi.org/10.1038/nature11019.

    Article  CAS  PubMed  Google Scholar 

  18. Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488:665–9. https://doi.org/10.1038/nature11308.

    Article  CAS  PubMed  Google Scholar 

  19. Wang L, Hu F, Cui Q, Qiao H, Li L, Geng T, et al. Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/beta-catenin signaling. Nat Commun. 2025;16:362 https://doi.org/10.1038/s41467-024-55431-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Park S, Wu L, Tu J, Yu W, Toh Y, Carmon KS, et al. Unlike LGR4, LGR5 potentiates Wnt-beta-catenin signaling without sequestering E3 ligases. Sci Signal. 2020;13. https://doi.org/10.1126/scisignal.aaz4051.

  21. Toh Y, Wu L, Park S, Wang A, Tu J, Yu W, et al. LGR4 and LGR5 form distinct homodimers that only LGR4 complexes with RNF43/ZNRF3 to provide high affinity binding of R-spondin ligands. Sci Rep. 2023;13:10796 https://doi.org/10.1038/s41598-023-37856-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gao Y, Kitagawa K, Hiramatsu Y, Kikuchi H, Isobe T, Shimada M, et al. Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis. Cancer Res. 2006;66:11623–31.

    Article  CAS  PubMed  Google Scholar 

  23. Yi J, Xiong W, Gong X, Bellister S, Ellis LM, Liu Q. Analysis of LGR4 receptor distribution in human and mouse tissues. PLoS ONE. 2013;8:e78144 https://doi.org/10.1371/journal.pone.0078144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gugger M, White R, Song S, Waser B, Cescato R, Riviere P, et al. GPR87 is an overexpressed G-protein coupled receptor in squamous cell carcinoma of the lung. Dis Markers. 2008;24:41–50.

    Article  CAS  PubMed  Google Scholar 

  25. Gong X, Yi J, Carmon KS, Crumbley CA, Xiong W, Thomas A, et al. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness. Oncogene. 2015;34:4692–701. https://doi.org/10.1038/onc.2014.417.

    Article  CAS  PubMed  Google Scholar 

  26. Yue Z, Yuan Z, Zeng L, Wang Y, Lai L, Li J, et al. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells. FASEB J. 2018;32:2422–37. https://doi.org/10.1096/fj.201700897R.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Junttila MR, Mao W, Wang X, Wang BE, Pham T, Flygare J, et al. Targeting LGR5+ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci Transl Med. 2015;7:314ra186 https://doi.org/10.1126/scitranslmed.aac7433.

    Article  PubMed  Google Scholar 

  28. Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA. 2008;105:13427–32. https://doi.org/10.1073/pnas.0805706105.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kobayashi S, Yamada-Okabe H, Suzuki M, Natori O, Kato A, Matsubara K, et al. LGR5-positive colon cancer stem cells interconvert with drug-resistant LGR5-negative cells and are capable of tumor reconstitution. Stem Cells. 2012;30:2631–44. https://doi.org/10.1002/stem.1257.

    Article  CAS  PubMed  Google Scholar 

  30. Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012;30:2378–86. https://doi.org/10.1002/stem.1233.

    Article  CAS  PubMed  Google Scholar 

  31. Huang PY, Kandyba E, Jabouille A, Sjolund J, Kumar A, Halliwill K, et al. Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma. Nat Genet. 2017;49:1624–32. https://doi.org/10.1038/ng.3957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shimokawa M, Ohta Y, Nishikori S, Matano M, Takano A, Fujii M, et al. Visualization and targeting of LGR5(+) human colon cancer stem cells. Nature. 2017;545:187–92. https://doi.org/10.1038/nature22081.

    Article  CAS  PubMed  Google Scholar 

  33. de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature. 2017;543:676–80. https://doi.org/10.1038/nature21713.

    Article  CAS  PubMed  Google Scholar 

  34. Kim SK, Kim SY, Kim JH, Roh SA, Cho DH, Kim YS, et al. A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients. Mol Oncol. 2014;8:1653–66. https://doi.org/10.1016/j.molonc.2014.06.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Leto SM, Grassi E, Avolio M, Vurchio V, Cottino F, Ferri M, et al. XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients. Nat Commun. 2024:15:7495–506. https://doi.org/10.1038/s41467-024-51909-2.

  36. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14:154–69. https://doi.org/10.1097/PPO.0b013e318172d704.

    Article  CAS  PubMed  Google Scholar 

  37. Dumontet C, Reichert JM, Senter PD, Lambert JM, Beck A. Antibody-drug conjugates come of age in oncology. Nat Rev Drug Discov. 2023;22:641–61. https://doi.org/10.1038/s41573-023-00709-2. e-pub ahead of print 20230612

    Article  CAS  PubMed  Google Scholar 

  38. Cui J, Toh Y, Park S, Yu W, Tu J, Wu L, et al. Drug conjugates of antagonistic R-spondin 4 mutant for simultaneous targeting of leucine-rich repeat-containing G protein-coupled receptors 4/5/6 for cancer treatment. J Med Chem. 2021;64:12572–81. https://doi.org/10.1021/acs.jmedchem.1c00395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tolcher AW. Antibody drug conjugates: lessons from 20 years of clinical experience. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO. Ann Oncol. 2016;27:2168–72. https://doi.org/10.1093/annonc/mdw424.

    Article  CAS  PubMed  Google Scholar 

  40. Bailly C. Irinotecan: 25 years of cancer treatment. Pharmacol Res. 2019;148:104398. https://doi.org/10.1016/j.phrs.2019.104398.

    Article  CAS  PubMed  Google Scholar 

  41. Lyski RD, Bou LB, Lau UY, Meyer DW, Cochran JH, Okeley NM, et al. Development of novel antibody-camptothecin conjugates. Mol Cancer Ther. 2021;20:329–39. https://doi.org/10.1158/1535-7163.MCT-20-0526.

    Article  CAS  PubMed  Google Scholar 

  42. Dennler P, Chiotellis A, Fischer E, Bregeon D, Belmant C, Gauthier L, et al. Transglutaminase-based chemo-enzymatic conjugation approach yields homogeneous antibody-drug conjugates. Bioconjug Chem. 2014;25:569–78. https://doi.org/10.1021/bc400574z.

    Article  CAS  PubMed  Google Scholar 

  43. Lhospice F, Bregeon D, Belmant C, Dennler P, Chiotellis A, Fischer E, et al. Site-specific conjugation of monomethyl auristatin E to Anti-CD30 antibodies improves their pharmacokinetics and therapeutic index in rodent models. Mol Pharm. 2015;12:1863–71. https://doi.org/10.1021/mp500666j.

    Article  CAS  PubMed  Google Scholar 

  44. Gong X, Carmon KS, Lin Q, Thomas A, Yi J, Liu Q. LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS ONE. 2012;7:e37137 https://doi.org/10.1371/journal.pone.0037137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jacob J, Francisco LE, Chatterjee T, Liang Z, Subramanian S, Liu QJ, et al. An antibody-drug conjugate targeting GPR56 demonstrates efficacy in preclinical models of colorectal cancer. Br J Cancer. 2023;128:1592–602. https://doi.org/10.1038/s41416-023-02192-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Strop P, Liu SH, Dorywalska M, Delaria K, Dushin RG, Tran TT, et al. Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates. Chem Biol. 2013;20:161–7. https://doi.org/10.1016/j.chembiol.2013.01.010.

    Article  CAS  PubMed  Google Scholar 

  47. Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016;22:5097–108. https://doi.org/10.1158/1078-0432.CCR-15-2822.

    Article  CAS  PubMed  Google Scholar 

  48. Peng WC, de Lau W, Madoori PK, Forneris F, Granneman JC, Clevers H, et al. Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and implications for signaling. PLoS One. 2013;8:e83110 https://doi.org/10.1371/journal.pone.0083110.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Anami Y, Xiong W, Gui X, Deng M, Zhang CC, Zhang N, et al. Enzymatic conjugation using branched linkers for constructing homogeneous antibody-drug conjugates with high potency. Org Biomol Chem. 2017;15:5635–42. https://doi.org/10.1039/c7ob01027c.

    Article  CAS  PubMed  Google Scholar 

  50. Saber H, Leighton JK. An FDA oncology analysis of antibody-drug conjugates. Regul Toxicol Pharmacol. 2015;71:444–52. https://doi.org/10.1016/j.yrtph.2015.01.014.

    Article  CAS  PubMed  Google Scholar 

  51. Gong X, Azhdarinia A, Ghosh SC, Xiong W, An Z, Liu Q, et al. LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence. Mol Cancer Ther. 2016;15:1580–90. https://doi.org/10.1158/1535-7163.MCT-16-0114.

    Article  CAS  PubMed  Google Scholar 

  52. Fumagalli A, Oost KC, Kester L, Morgner J, Bornes L, Bruens L, et al. Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer. Cell Stem Cell. 2020;26:569–578 e567. https://doi.org/10.1016/j.stem.2020.02.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Nessler I, Menezes B, Thurber GM. Key metrics to expanding the pipeline of successful antibody-drug conjugates. Trends Pharm Sci. 2021;42:803–12. https://doi.org/10.1016/j.tips.2021.07.005.

    Article  CAS  PubMed  Google Scholar 

  54. Tarcsa E, Guffroy MR, Falahatpisheh H, Phipps C, Kalvass JC. Antibody-drug conjugates as targeted therapies: Are we there yet? A critical review of the current clinical landscape. Drug Discov Today Technol. 2020;37:13–22. https://doi.org/10.1016/j.ddtec.2020.07.002.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Mr. Jack Adams of UTHealth-Houston for drawing the structure of PEG2-bis-PE3-azido-DBCO-PEG8-VKG-CPT2.

Funding

This work was supported in part by funding from the Cancer Prevention and Research Institute of Texas (CPRIT) RP220169 (to QJL and KSC), RP210119 (to QJL), National Cancer Institute (NCI) R01CA226894 and R21 CA282378 (to KSC), and the Janice David Gordon for Bowel Cancer Research Endowment (to QJL).

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Authors and Affiliations

  1. Center for Translational Cancer Research, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA

    Yukimatsu Toh, Ling Wu, Jianghua Tu, Zhengdong Liang, Adela M. Aldana, Jake J. Wen, Li Li, Sheng Pan, Kendra S. Carmon & Qingyun J. Liu

  2. Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA

    Julie H. Rowe

  3. Department of Comparative Medicine, Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, Bastrop, TX, USA

    Martha E. Hensel, Carolyn L. Hodo & Rick A. Finch

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  1. Yukimatsu Toh
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Contributions

YT, KSC and QJL devised the concept. YT, LW, JT, ZL, AMA, JJW, LL, SP, JHR, MEH, CLH, RAF, KSC and QJL designed, performed, and analyzed experiments. YT and QJL wrote the manuscript. All coauthors reviewed and approved of the final manuscript.

Corresponding author

Correspondence to Qingyun J. Liu.

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Competing interests

The authors declare the following competing financial interest(s): KSC and QJL and the Regents of the University of Texas have filed a patent application related to this project.

Ethics approval

All methods in this study were performed in accordance with the relevant guidelines and regulations. All animal experiments were approved by the Institutional Animal Care and Use Committee of the University of Texas at Houston (Protocol number AWC-22-0080, AWC-20-0144, and AWC-23-0106).

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Supplementary information

41416_2025_3121_MOESM1_ESM.pdf (download PDF )

Supplementary Figure S1. Coomassie blue staining image of purified R462 and R465 under reducing (left side) and non reduction condition (right side).

41416_2025_3121_MOESM2_ESM.pdf (download PDF )

Supplementary Figure S2. In vitro cytotoxicity of R462-CPT2 and R465-CPT2 in HEK293T cells and HEK293T cells expressing LGR4, LGR5, or LGR6. a

Supplementary Figure S3. Pharmacokinetics of R462 and R462-CPT in mice. (download PDF )

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Toh, Y., Wu, L., Tu, J. et al. Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer. Br J Cancer 133, 1218–1228 (2025). https://doi.org/10.1038/s41416-025-03121-2

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