Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

Amanda M. Nash; Maria I. Jarvis; Samira Aghlara-Fotovat; Sudip Mukherjee; Andrea Hernandez; Andrew D. Hecht; Peter D. Rios; Sofia Ghani; Ira Joshi; Douglas Isa; Yufei Cui; Shirin Nouraein; Jared Z. Lee; Chunyu Xu; David Y. Zhang; Rahul A. Sheth; Weiyi Peng; Jose Oberholzer; Oleg A. Igoshin; Amir A. Jazaeri; Omid Veiseh

doi:10.1126/sciadv.abm1032

Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

Amanda M. Nash, Maria I. Jarvis, Samira Aghlara-Fotovat, Sudip Mukherjee, Andrea Hernandez, Andrew D. Hecht, Peter D. Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Yufei Cui, Shirin Nouraein, Jared Z. Lee, Chunyu Xu, David Y. Zhang, Rahul A. Sheth, Weiyi Peng, Jose Oberholzer, Oleg A. Igoshin, Amir A. JazaeriOmid Veiseh

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32 Scopus citations

Abstract

Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.

Original language	English (US)
Article number	eabm1032
Journal	Science Advances
Volume	8
Issue number	9
DOIs	https://doi.org/10.1126/sciadv.abm1032
State	Published - Mar 2022

ASJC Scopus subject areas

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MD Anderson CCSG core facilities

Research Animal Support Facility
Flow Cytometry and Cellular Imaging Facility

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Nash, A. M., Jarvis, M. I., Aghlara-Fotovat, S., Mukherjee, S., Hernandez, A., Hecht, A. D., Rios, P. D., Ghani, S., Joshi, I., Isa, D., Cui, Y., Nouraein, S., Lee, J. Z., Xu, C., Zhang, D. Y., Sheth, R. A., Peng, W., Oberholzer, J., Igoshin, O. A., ... Veiseh, O. (2022). Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors. Science Advances, 8(9), Article eabm1032. https://doi.org/10.1126/sciadv.abm1032

Nash, AM, Jarvis, MI, Aghlara-Fotovat, S, Mukherjee, S, Hernandez, A, Hecht, AD, Rios, PD, Ghani, S, Joshi, I, Isa, D, Cui, Y, Nouraein, S, Lee, JZ, Xu, C, Zhang, DY, Sheth, RA, Peng, W, Oberholzer, J, Igoshin, OA, Jazaeri, AA & Veiseh, O 2022, 'Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors', Science Advances, vol. 8, no. 9, eabm1032. https://doi.org/10.1126/sciadv.abm1032

@article{c8c266f0b2074c5d9db24c0608db9a18,

title = "Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors",

abstract = "Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.",

author = "Nash, {Amanda M.} and Jarvis, {Maria I.} and Samira Aghlara-Fotovat and Sudip Mukherjee and Andrea Hernandez and Hecht, {Andrew D.} and Rios, {Peter D.} and Sofia Ghani and Ira Joshi and Douglas Isa and Yufei Cui and Shirin Nouraein and Lee, {Jared Z.} and Chunyu Xu and Zhang, {David Y.} and Sheth, {Rahul A.} and Weiyi Peng and Jose Oberholzer and Igoshin, {Oleg A.} and Jazaeri, {Amir A.} and Omid Veiseh",

note = "Funding Information: This work was supported by Cancer Prevention Research Institute of Texas grant RR160047 (to O.V.), Avenge Bio Sponsored Research Agreement to Rice University (to O.V.) and CellTrans Inc. (to J.O.), Emerson Collective (to A.A.J. and W.P.), Welch Foundation (to O.A.I. and A.D.H.), Rice University Academy Fellowship (to M.I.J.), National Science Foundation grant 1842494 (to A.M.N.), and National Institute of Health grant 1RO1DK120459-01 (to A.M.N. and O.V.). Publisher Copyright: Copyright {\textcopyright} 2022 The Authors.",

year = "2022",

month = mar,

doi = "10.1126/sciadv.abm1032",

language = "English (US)",

volume = "8",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "9",

}

TY - JOUR

T1 - Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

AU - Nash, Amanda M.

AU - Jarvis, Maria I.

AU - Aghlara-Fotovat, Samira

AU - Mukherjee, Sudip

AU - Hernandez, Andrea

AU - Hecht, Andrew D.

AU - Rios, Peter D.

AU - Ghani, Sofia

AU - Joshi, Ira

AU - Isa, Douglas

AU - Cui, Yufei

AU - Nouraein, Shirin

AU - Lee, Jared Z.

AU - Xu, Chunyu

AU - Zhang, David Y.

AU - Sheth, Rahul A.

AU - Peng, Weiyi

AU - Oberholzer, Jose

AU - Igoshin, Oleg A.

AU - Jazaeri, Amir A.

AU - Veiseh, Omid

N1 - Funding Information: This work was supported by Cancer Prevention Research Institute of Texas grant RR160047 (to O.V.), Avenge Bio Sponsored Research Agreement to Rice University (to O.V.) and CellTrans Inc. (to J.O.), Emerson Collective (to A.A.J. and W.P.), Welch Foundation (to O.A.I. and A.D.H.), Rice University Academy Fellowship (to M.I.J.), National Science Foundation grant 1842494 (to A.M.N.), and National Institute of Health grant 1RO1DK120459-01 (to A.M.N. and O.V.). Publisher Copyright: Copyright © 2022 The Authors.

PY - 2022/3

Y1 - 2022/3

N2 - Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.

AB - Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.

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JF - Science Advances

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ER -

Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors

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ASJC Scopus subject areas

MD Anderson CCSG core facilities

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