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Comment
. 2020 Dec 1;26(23):6080-6082.
doi: 10.1158/1078-0432.CCR-20-3250. Epub 2020 Oct 1.

Interleukin-12 Message in a Bottle

Assunta Cirella  1   2 , Pedro Berraondo  1   2   3 , Claudia Augusta Di Trani  1   2 , Ignacio Melero  4   2   3   5
Affiliations
Comment

Interleukin-12 Message in a Bottle

Assunta Cirella et al. Clin Cancer Res. .

Abstract

IL12 is a very potent cancer immunotherapy agent, but is difficult to harness safely if given systemically. Local gene transfer aims to confine the effects of IL12 to malignant tissues, thus avoiding toxicity. Lipid-nanoparticle mRNA achieves IL12 expression and efficacy in mouse models, opening the way to an ongoing trial.See related article by Hewitt et al., p. 6284.

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  • Intratumoral IL12 mRNA Therapy Promotes TH1 Transformation of the Tumor Microenvironment.
    Hewitt SL, Bailey D, Zielinski J, Apte A, Musenge F, Karp R, Burke S, Garcon F, Mishra A, Gurumurthy S, Watkins A, Arnold K, Moynihan J, Clancy-Thompson E, Mulgrew K, Adjei G, Deschler K, Potz D, Moody G, Leinster DA, Novick S, Sulikowski M, Bagnall C, Martin P, Lapointe JM, Si H, Morehouse C, Sedic M, Wilkinson RW, Herbst R, Frederick JP, Luheshi N. Hewitt SL, et al. Clin Cancer Res. 2020 Dec 1;26(23):6284-6298. doi: 10.1158/1078-0432.CCR-20-0472. Epub 2020 Aug 17. Clin Cancer Res. 2020. PMID: 32817076

References

    1. Hewitt SL, Bailey D, Zielinski J, Apte A, Musenge F, Karp R, et al. Intratumoral interleukin-12 mRNA therapy promotes TH1 transformation of the tumor microenvironment. Clin Cancer Res. 2020;26:6284–98.
    1. Hewitt SL, Bai A, Bailey D, Ichikawa K, Zielinski J, Karp R, et al. Durable anticancer immunity from intratumoral administration of IL-23, IL-36gamma, and OX40L mRNAs. Sci Transl Med. 2019;11:eaat9143.
    1. Li Y, Su Z, Zhao W, Zhang X, Momin N, Zhang C, et al. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat Cancer. 2020;1:882–93.
    1. Berraondo P, Etxeberria I, Ponz-Sarvise M, Melero I. Revisiting interleukin-12 as a cancer immunotherapy agent. Clin Cancer Res. 2018;24:2716–8.
    1. Algazi AP, Twitty CG, Tsai KK, Le M, Pierce R, Browning E, et al. Phase II trial of IL-12 plasmid transfection and PD-1 blockade in immunologically quiescent melanoma. Clin Cancer Res. 2020;26:2827–37.

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