Review
. 2021 May; 12:617365.
doi: 10.3389/fimmu.2021.617365.

Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ

Renske J E van den Bijgaart 1 Fabian Schuurmans 1 Jurgen J Fütterer 2 Marcel Verheij 1 Lenneke A M Cornelissen 1 Gosse J Adema 1 
Affiliations
  • PMID: 33936033
  •     142 References
  •     4 citations

Abstract

In situ tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains in situ. This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of in situ cancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achieve in situ cancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together with in situ ablation to boost anti-tumor immunity for local and systemic tumor control.

Keywords: combination therapy; immune activation; in situ cancer vaccination; multifunctional antibodies; tumor ablation.

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Cancer Res, 2011 Jul 27; 71(20). PMID: 21788345    Free PMC article.
High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy.
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Clin Cancer Res, 2019 Oct 17; 26(5). PMID: 31615935    Free PMC article.
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Andrew J Rech, Hannah Dada, +4 authors, Robert H Vonderheide.
Cancer Res, 2018 May 31; 78(15). PMID: 29844122    Free PMC article.
PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor.
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Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell-Mediated Tumor Immunity.
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Cancer Res, 2018 Apr 29; 78(13). PMID: 29703719
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Cryotherapy with concurrent CpG oligonucleotide treatment controls local tumor recurrence and modulates HER2/neu immunity.
Jesse J Veenstra, Heather M Gibson, +4 authors, Wei-Zen Wei.
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A Novel TGFβ Trap Blocks Chemotherapeutics-Induced TGFβ1 Signaling and Enhances Their Anticancer Activity in Gynecologic Cancers.
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CD137/OX40 Bispecific Antibody Induces Potent Antitumor Activity that Is Dependent on Target Coengagement.
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The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation.
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Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response.
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Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment.
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Dendritic cells: tools and targets for antitumor vaccination.
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Combination of radiotherapy and suppression of Tregs enhances abscopal antitumor effect and inhibits metastasis in rectal cancer.
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Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol.
Bart Geboers, Florentine E F Timmer, +16 authors, On Behalf Of The Dutch Pancreatic Cancer Group.
Cancers (Basel), 2021 Aug 08; 13(15). PMID: 34359801    Free PMC article.
Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside.
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How Compatible Are Immune Checkpoint Inhibitors and Thermal Ablation for Liver Metastases?
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