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Charting roadmaps towards novel and safe synergistic immunotherapy combinations

Nature Cancer volume 3, pages 665–680 (2022)Cite this article

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Abstract

Checkpoint inhibitor-based cancer immunotherapy is often combined in the clinic with other immunotherapy strategies, targeted therapies, chemotherapy or standard-of-care treatments to achieve superior therapeutic efficacy. The large number of immunotherapy combinations that are currently undergoing clinical testing necessitate the establishment of faithful criteria to prioritize optimal combinations with evidence of synergy, to determine their safety and optimal sequence of administration and to identify biomarkers of therapy resistance and response. In this review, we focus on recent developments in immunotherapy combinations and reflect on how combinations should be optimized to maximize the impact of immunotherapy in clinical oncology.

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Fig. 1: Functional categories of agents to design immunotherapy combinations.
Fig. 2: Bispecific compounds.
Fig. 3: Tumor immunosuppressive cytokines.
Fig. 4: Optimizing radiotherapy in combination with immunotherapy.

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Acknowledgements

For funding, our group is supported by PID2020-112892RB funded by MICIN/AEI/10.13039/501100011033 and SAF2017-83267-C2-1-R funded by MICIN/AEI/10.13039/501100011033/ and by FEDER ‘Una manera de hacer Europa’, the Fundación de la Asociación Española Contra el Cáncer (AECC) (HR21-00083), the Fundación La Caixa and Fundación BBVA, the Instituto de Salud Carlos III (PI20/00002 and PI19/01128), cofinanced by the Fondos FEDER ‘A way to make Europe’ and Joint Translational Call for Proposals 2015 (JTC 2015), TRANSCAN456 2 (code TRS-2016-00000371) and the Gobierno de Navarra Proyecto LINTERNA (reference 0011-1411-2020-000075). M.F.S. receives a Miguel Servet I (MS17/00196) contract from the Instituto de Salud Carlos III cofinanced by the Fondo Social Europeo ‘Investing in your future’ and a grant from Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria (PI19/00668).

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Authors and Affiliations

  1. Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain

    Miguel F. Sanmamed, Pedro Berraondo, Maria E. Rodriguez-Ruiz & Ignacio Melero

  2. Navarra Institute for Health Research (IDISNA), Pamplona, Spain

    Miguel F. Sanmamed, Pedro Berraondo, Maria E. Rodriguez-Ruiz & Ignacio Melero

  3. Departments of Oncology and Immunology, Clínica Universidad de Navarra, Pamplona, Spain

    Miguel F. Sanmamed, Maria E. Rodriguez-Ruiz & Ignacio Melero

  4. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, Spain

    Miguel F. Sanmamed, Pedro Berraondo & Ignacio Melero

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  1. Miguel F. Sanmamed
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  2. Pedro Berraondo
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  3. Maria E. Rodriguez-Ruiz
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Corresponding author

Correspondence to Ignacio Melero.

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Competing interests

Regarding potential conflicts of interest, I.M. acknowledges grants from Roche, Alligator, Genmab, BMS, AstraZeneca, PharmaMar and Bioncotech, as well as consultancy fees from BMS, Roche, Genmab, Numab, Gossamer, Alligator, AstraZeneca, Pieris, HotSpot and PharmaMar. M.F.S. receives a grant from Roche. No disclosures were reported by the other authors.

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Sanmamed, M.F., Berraondo, P., Rodriguez-Ruiz, M.E. et al. Charting roadmaps towards novel and safe synergistic immunotherapy combinations. Nat Cancer 3, 665–680 (2022). https://doi.org/10.1038/s43018-022-00401-1

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