Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. / Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc; Brennen, W Nathaniel; Dalrymple, Susan; Dach, Ingrid; Olesen, Claus; Gurel, Bora; DeMarzo, Angelo M; Wilding, George; Carducci, Michael A; Dionne, Craig A; Møller, Jesper Vuust; Nissen, Poul; Christensen, Søren Brøgger; Isaacs, John T.

In: Science Translational Medicine, Vol. 4, No. 140, 27.06.2012, p. 140ra86.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Denmeade, SR, Mhaka, AM, Rosen, DM, Brennen, WN, Dalrymple, S, Dach, I, Olesen, C, Gurel, B, DeMarzo, AM, Wilding, G, Carducci, MA, Dionne, CA, Møller, JV, Nissen, P, Christensen, SB & Isaacs, JT 2012, 'Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy', Science Translational Medicine, vol. 4, no. 140, pp. 140ra86. https://doi.org/10.1126/scitranslmed.3003886

APA

Denmeade, S. R., Mhaka, A. M., Rosen, D. M., Brennen, W. N., Dalrymple, S., Dach, I., Olesen, C., Gurel, B., DeMarzo, A. M., Wilding, G., Carducci, M. A., Dionne, C. A., Møller, J. V., Nissen, P., Christensen, S. B., & Isaacs, J. T. (2012). Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. Science Translational Medicine, 4(140), 140ra86. https://doi.org/10.1126/scitranslmed.3003886

Vancouver

Denmeade SR, Mhaka AM, Rosen DM, Brennen WN, Dalrymple S, Dach I et al. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. Science Translational Medicine. 2012 Jun 27;4(140):140ra86. https://doi.org/10.1126/scitranslmed.3003886

Author

Denmeade, Samuel R ; Mhaka, Annastasiah M ; Rosen, D Marc ; Brennen, W Nathaniel ; Dalrymple, Susan ; Dach, Ingrid ; Olesen, Claus ; Gurel, Bora ; DeMarzo, Angelo M ; Wilding, George ; Carducci, Michael A ; Dionne, Craig A ; Møller, Jesper Vuust ; Nissen, Poul ; Christensen, Søren Brøgger ; Isaacs, John T. / Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. In: Science Translational Medicine. 2012 ; Vol. 4, No. 140. pp. 140ra86.

Bibtex

@article{404fcdd919d44057ba387aa5e304aaa9,
title = "Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy",
abstract = "Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.",
author = "Denmeade, {Samuel R} and Mhaka, {Annastasiah M} and Rosen, {D Marc} and Brennen, {W Nathaniel} and Susan Dalrymple and Ingrid Dach and Claus Olesen and Bora Gurel and DeMarzo, {Angelo M} and George Wilding and Carducci, {Michael A} and Dionne, {Craig A} and M{\o}ller, {Jesper Vuust} and Poul Nissen and Christensen, {S{\o}ren Br{\o}gger} and Isaacs, {John T}",
year = "2012",
month = jun,
day = "27",
doi = "10.1126/scitranslmed.3003886",
language = "English",
volume = "4",
pages = "140ra86",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "140",

}

RIS

TY - JOUR

T1 - Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy

AU - Denmeade, Samuel R

AU - Mhaka, Annastasiah M

AU - Rosen, D Marc

AU - Brennen, W Nathaniel

AU - Dalrymple, Susan

AU - Dach, Ingrid

AU - Olesen, Claus

AU - Gurel, Bora

AU - DeMarzo, Angelo M

AU - Wilding, George

AU - Carducci, Michael A

AU - Dionne, Craig A

AU - Møller, Jesper Vuust

AU - Nissen, Poul

AU - Christensen, Søren Brøgger

AU - Isaacs, John T

PY - 2012/6/27

Y1 - 2012/6/27

N2 - Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.

AB - Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.

U2 - 10.1126/scitranslmed.3003886

DO - 10.1126/scitranslmed.3003886

M3 - Journal article

C2 - 22745436

VL - 4

SP - 140ra86

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 140

ER -

ID: 38405956