Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles

Cristianne J.F. Rijcken; Federica De Lorenzi; Ilaria Biancacci; Rob G.J.M. Hanssen; Marielle Thewissen; Qizhi Hu; Florence Atrafi; Rob M.J. Liskamp; Ron H.J. Mathijssen; Iris H.C. Miedema; C. Willemien Menke - van der Houven van Oordt; Guus A.M.S. van Dongen; Danielle J. Vugts; Matt Timmers; Wim E. Hennink; Twan Lammers

doi:10.1016/j.addr.2022.114613

Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles

Cristianne J.F. Rijcken^*, Federica De Lorenzi, Ilaria Biancacci, Rob G.J.M. Hanssen, Marielle Thewissen, Qizhi Hu, Florence Atrafi, Rob M.J. Liskamp, Ron H.J. Mathijssen, Iris H.C. Miedema, C. Willemien Menke - van der Houven van Oordt, Guus A.M.S. van Dongen, Danielle J. Vugts, Matt Timmers, Wim E. Hennink, Twan Lammers

^*Corresponding author for this work

Medical Oncology

Research output: Contribution to journal › Review article › Academic › peer-review

19 Citations (Scopus)

Abstract

Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLac_n) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLac_n CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.

Original language	English
Article number	114613
Journal	Advanced Drug Delivery Reviews
Volume	191
DOIs	https://doi.org/10.1016/j.addr.2022.114613
Publication status	Published - Dec 2022

Bibliographical note

Acknowledgements
CJFR, RH, MTh, QH and MTi are employees of Cristal Therapeutics. The other authors have no competing interest to disclose. The authors gratefully acknowledge financial support by the European Research Council (TL – ERC Consolidator Grant 864121: Meta-Targeting), the European Fund for Regional Development (FDL, TL – TAKTIRA: Project number: EFRE-0801767)), the German Research Foundation (IB, TL – DFG: GRK2375 (Project number: 331065168) and SFB1066), Horizon SME grant (784127), and the German Federal Ministry of Research and Education (TL; BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project number 16GW0319K).

Publisher Copyright: © 2022 Elsevier B.V.

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Rijcken, C. J. F., De Lorenzi, F., Biancacci, I., Hanssen, R. G. J. M., Thewissen, M., Hu, Q., Atrafi, F., Liskamp, R. M. J., Mathijssen, R. H. J., Miedema, I. H. C., Menke - van der Houven van Oordt, C. W., van Dongen, G. A. M. S., Vugts, D. J., Timmers, M., Hennink, W. E., & Lammers, T. (2022). Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles. Advanced Drug Delivery Reviews, 191, Article 114613. https://doi.org/10.1016/j.addr.2022.114613

@article{b293c58ff5fd4185ba8e5beb96a2d171,

title = "Design, development and clinical translation of CriPec{\textregistered}-based core-crosslinked polymeric micelles",

abstract = "Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec{\textregistered} technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLacn CCPM based on CriPec{\textregistered} technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.",

author = "Rijcken, {Cristianne J.F.} and {De Lorenzi}, Federica and Ilaria Biancacci and Hanssen, {Rob G.J.M.} and Marielle Thewissen and Qizhi Hu and Florence Atrafi and Liskamp, {Rob M.J.} and Mathijssen, {Ron H.J.} and Miedema, {Iris H.C.} and {Menke - van der Houven van Oordt}, {C. Willemien} and {van Dongen}, {Guus A.M.S.} and Vugts, {Danielle J.} and Matt Timmers and Hennink, {Wim E.} and Twan Lammers",

note = "Acknowledgements CJFR, RH, MTh, QH and MTi are employees of Cristal Therapeutics. The other authors have no competing interest to disclose. The authors gratefully acknowledge financial support by the European Research Council (TL – ERC Consolidator Grant 864121: Meta-Targeting), the European Fund for Regional Development (FDL, TL – TAKTIRA: Project number: EFRE-0801767)), the German Research Foundation (IB, TL – DFG: GRK2375 (Project number: 331065168) and SFB1066), Horizon SME grant (784127), and the German Federal Ministry of Research and Education (TL; BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project number 16GW0319K). Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = dec,

doi = "10.1016/j.addr.2022.114613",

language = "English",

volume = "191",

journal = "Advanced Drug Delivery Reviews",

issn = "0169-409X",

publisher = "Elsevier",

}

Rijcken, CJF, De Lorenzi, F, Biancacci, I, Hanssen, RGJM, Thewissen, M, Hu, Q, Atrafi, F, Liskamp, RMJ, Mathijssen, RHJ, Miedema, IHC, Menke - van der Houven van Oordt, CW, van Dongen, GAMS, Vugts, DJ, Timmers, M, Hennink, WE & Lammers, T 2022, 'Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles', Advanced Drug Delivery Reviews, vol. 191, 114613. https://doi.org/10.1016/j.addr.2022.114613

TY - JOUR

T1 - Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles

AU - Rijcken, Cristianne J.F.

AU - De Lorenzi, Federica

AU - Biancacci, Ilaria

AU - Hanssen, Rob G.J.M.

AU - Thewissen, Marielle

AU - Hu, Qizhi

AU - Atrafi, Florence

AU - Liskamp, Rob M.J.

AU - Mathijssen, Ron H.J.

AU - Miedema, Iris H.C.

AU - Menke - van der Houven van Oordt, C. Willemien

AU - van Dongen, Guus A.M.S.

AU - Vugts, Danielle J.

AU - Timmers, Matt

AU - Hennink, Wim E.

AU - Lammers, Twan

N1 - Acknowledgements CJFR, RH, MTh, QH and MTi are employees of Cristal Therapeutics. The other authors have no competing interest to disclose. The authors gratefully acknowledge financial support by the European Research Council (TL – ERC Consolidator Grant 864121: Meta-Targeting), the European Fund for Regional Development (FDL, TL – TAKTIRA: Project number: EFRE-0801767)), the German Research Foundation (IB, TL – DFG: GRK2375 (Project number: 331065168) and SFB1066), Horizon SME grant (784127), and the German Federal Ministry of Research and Education (TL; BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project number 16GW0319K). Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/12

Y1 - 2022/12

N2 - Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLacn CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.

AB - Nanomedicines are used to improve the efficacy and safety of pharmacotherapeutic interventions. Unraveling the biological behavior of nanomedicines, including their biodistribution and target site accumulation, is essential to establish design criteria that contribute to superior performance. CriPec® technology is based on amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers, which are designed to upon self-assembly covalently entrap active pharmaceutical ingredients (API) in core-crosslinked polymeric micelles (CCPM). Key features of CCPM are a prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in the majority of healthy tissues. Proprietary hydrolysable linkers allow for tunable and sustained release of entrapped API, including hydrophobic and hydrophilic small molecules, as well as peptides and oligonucleotides. Preclinical imaging experiments provided valuable information on their tumor and tissue accumulation and distribution, as well as on uptake by cancer, healthy and immune cells. The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models. In the clinic, CPC634 also demonstrated favorable pharmacokinetics, good tolerability, signs of efficacy, and enhanced localization in tumor tissue as compared to conventional docetaxel. PET imaging of radiolabeled CPC634 showed quantifiable accumulation in ∼50 % of tumors and metastases in advanced-stage cancer patients, and demonstrated potential for use in a theranostic setting even when applied at a companion diagnostic dose. Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLacn CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy.

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DO - 10.1016/j.addr.2022.114613

M3 - Review article

C2 - 36343757

AN - SCOPUS:85141467959

SN - 0169-409X

VL - 191

JO - Advanced Drug Delivery Reviews

JF - Advanced Drug Delivery Reviews

M1 - 114613

ER -

Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles

Abstract

Bibliographical note

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