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IMMUNOTHERAPY

ISACs take a Toll on tumors

Nature Cancer volume 2, pages 12–13 (2021)Cite this article

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Immunostimulatory agents such as Toll-like receptor (TLR) agonists have shown promising antitumor efficacy but are associated with therapy-related toxicities when delivered systemically. Immune-stimulating antibody conjugates are now shown to deliver TLR agonists with potent preclinical antitumor activities.

Immunotherapies, including immune-checkpoint inhibitors that target the immunoinhibitory receptor PD-1 and its ligand PD-L1, have shown substantial anti-tumor immune responses in diverse tumor types. However, a large fraction of patients still do not benefit from these therapies, and the lack of efficacy may be attributed to low infiltration of immune cells into tumors or deficient priming of adaptive anti-tumor immunity. The anti-tumor activity of immune-checkpoint inhibitors can be improved through combination with innate immunity–stimulating agents, including TLR agonists1. However, systemic delivery of TLR agonists is associated with undesired toxicity, and intratumoral injection, which improves the tolerability of these therapeutic agents, has practical limitations, such as tumor size and accessibility, and this may narrow their potential for clinical use. In this issue of Nature Cancer, Ackerman et al. describe an alternative strategy for delivering agonists of TLR7 and TLR8 (TLR7/8) to tumors through systemic administration of immune-stimulating antibody conjugates (ISACs)2.

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Fig. 1: ISACs: two hits against cancer with one antibody.

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Authors and Affiliations

  1. Innate Pharma Research Laboratories, Innate Pharma, Marseille, France

    Olivier Demaria & Eric Vivier

  2. Aix Marseille University, CNRS, INSERM, CIML, Marseille, France

    Eric Vivier

  3. Assistance Publique des Hôpitaux de Marseille, Hôpital de la Timone, Immunology, Marseille-Immunopôle, Marseille, France

    Eric Vivier

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  1. Olivier Demaria
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  2. Eric Vivier
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Correspondence to Olivier Demaria.

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O.D. and E.V. are employees of Innate Pharma.

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Demaria, O., Vivier, E. ISACs take a Toll on tumors. Nat Cancer 2, 12–13 (2021). https://doi.org/10.1038/s43018-020-00152-x

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