Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine

Jiawei Wang; Lian Li; Jiyuan Yang; Phillip M. Clair; Martha J. Glenn; Deborah M. Stephens; D. Christopher Radford; Ken M. Kosak; Michael W. Deininger; Paul J. Shami; Jindřich Kopeček

doi:10.1016/j.nano.2018.12.011

Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine

Jiawei Wang, Lian Li, Jiyuan Yang, Phillip M. Clair, Martha J. Glenn, Deborah M. Stephens, D. Christopher Radford, Ken M. Kosak, Michael W. Deininger, Paul J. Shami, Jindřich Kopeček

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab’-MORF1 (anti-CD20 Fab’ fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) _X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies.

Original language	English
Pages (from-to)	217-225
Number of pages	9
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	16
DOIs	https://doi.org/10.1016/j.nano.2018.12.011
State	Published - Feb 2019
Externally published	Yes

Funding

Acknowledgments: The work was supported in part by NIH grant RO1 GM95606 (to JK) from the National Institute of General Medical Sciences , Huntsman Cancer Institute (award No. 180303 ), and the University of Utah Research Foundation . We acknowledge support of funds from grant P30 CS042014 awarded to Huntsman Cancer Institute and to the ET Program at Huntsman Cancer Institute.

Funders	Funder number
University of Utah Research Foundation	P30 CS042014
National Institutes of Health
National Institute of General Medical Sciences	R01GM095606
Huntsman Cancer Institute	180303

Keywords

Apoptosis
B cell lymphoma
CD20
Drug-free macromolecular therapeutics
Nanomedicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.nano.2018.12.011

Cite this

Wang, J., Li, L., Yang, J., Clair, P. M., Glenn, M. J., Stephens, D. M., Radford, D. C., Kosak, K. M., Deininger, M. W., Shami, P. J., & Kopeček, J. (2019). Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine. Nanomedicine: Nanotechnology, Biology, and Medicine, 16, 217-225. https://doi.org/10.1016/j.nano.2018.12.011

@article{a3a4627dd2744c5bae02e0d16758a937,

title = "Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine",

abstract = " Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab{\textquoteright}-MORF1 (anti-CD20 Fab{\textquoteright} fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies.",

keywords = "Apoptosis, B cell lymphoma, CD20, Drug-free macromolecular therapeutics, Nanomedicine",

author = "Jiawei Wang and Lian Li and Jiyuan Yang and Clair, {Phillip M.} and Glenn, {Martha J.} and Stephens, {Deborah M.} and Radford, {D. Christopher} and Kosak, {Ken M.} and Deininger, {Michael W.} and Shami, {Paul J.} and Jind{\v r}ich Kope{\v c}ek",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = feb,

doi = "10.1016/j.nano.2018.12.011",

language = "English",

volume = "16",

pages = "217--225",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

issn = "1549-9634",

publisher = "Elsevier",

}

Wang, J, Li, L, Yang, J, Clair, PM, Glenn, MJ, Stephens, DM, Radford, DC, Kosak, KM, Deininger, MW, Shami, PJ & Kopeček, J 2019, 'Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 16, pp. 217-225. https://doi.org/10.1016/j.nano.2018.12.011

Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine. / Wang, Jiawei; Li, Lian; Yang, Jiyuan et al.
In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 16, 02.2019, p. 217-225.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine

AU - Wang, Jiawei

AU - Li, Lian

AU - Yang, Jiyuan

AU - Clair, Phillip M.

AU - Glenn, Martha J.

AU - Stephens, Deborah M.

AU - Radford, D. Christopher

AU - Kosak, Ken M.

AU - Deininger, Michael W.

AU - Shami, Paul J.

AU - Kopeček, Jindřich

PY - 2019/2

Y1 - 2019/2

N2 - Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab’-MORF1 (anti-CD20 Fab’ fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies.

AB - Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab’-MORF1 (anti-CD20 Fab’ fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies.

KW - Apoptosis

KW - B cell lymphoma

KW - CD20

KW - Drug-free macromolecular therapeutics

KW - Nanomedicine

UR - http://www.scopus.com/inward/record.url?scp=85060762825&partnerID=8YFLogxK

U2 - 10.1016/j.nano.2018.12.011

DO - 10.1016/j.nano.2018.12.011

M3 - Article

C2 - 30639670

AN - SCOPUS:85060762825

SN - 1549-9634

VL - 16

SP - 217

EP - 225

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

ER -

Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this