Targeting Cancer Heterogeneity with Immune Responses Driven by Oncolytic Peptides

Ilio Vitale; Takahiro Yamazaki; Erik Wennerberg; Baldur Sveinbjørnsson; Øystein Rekdal; Sandra Demaria; Lorenzo Galluzzi

doi:10.1016/j.trecan.2020.12.012

Targeting Cancer Heterogeneity with Immune Responses Driven by Oncolytic Peptides

Trends Cancer. 2021 Jun;7(6):557-572. doi: 10.1016/j.trecan.2020.12.012. Epub 2021 Jan 11.

Authors

Ilio Vitale¹, Takahiro Yamazaki², Erik Wennerberg³, Baldur Sveinbjørnsson⁴, Øystein Rekdal⁵, Sandra Demaria⁶, Lorenzo Galluzzi⁷

Affiliations

¹ Italian Institute for Genomic Medicine (IIGM), Istituto Di Ricovero e Cura a Carattere Scientifico (IRCSS) Candiolo, Torino, Italy; Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO)-IRCCS, Candiolo, Italy.
² Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
³ Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
⁴ Lytix Biopharma, Oslo, Norway; Department of Medical Biology, University of Tromsø, Tromsø, Norway; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
⁵ Lytix Biopharma, Oslo, Norway; Department of Medical Biology, University of Tromsø, Tromsø, Norway.
⁶ Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA.
⁷ Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA; Université de Paris, Paris, France. Electronic address: deadoc80@gmail.com.

PMID: 33446447
DOI: 10.1016/j.trecan.2020.12.012

Abstract

Accumulating preclinical and clinical evidence indicates that high degrees of heterogeneity among malignant cells constitute a considerable obstacle to the success of cancer therapy. This calls for the development of approaches that operate - or enable established treatments to operate - despite such intratumoral heterogeneity (ITH). In this context, oncolytic peptides stand out as promising therapeutic tools based on their ability to drive immunogenic cell death associated with robust anticancer immune responses independently of ITH. We review the main molecular and immunological pathways engaged by oncolytic peptides, and discuss potential approaches to combine these agents with modern immunotherapeutics in support of superior tumor-targeting immunity and efficacy in patients with cancer.

Keywords: CD8(+) cytotoxic T lymphocytes; LL-37; LTX-315; NK cells; antimicrobial peptides; genomic instability; immune checkpoint inhibitors.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Antigens, Neoplasm / immunology
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cell Line, Tumor
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Drug Synergism
Humans
Immune Checkpoint Inhibitors / pharmacology*
Immune Checkpoint Inhibitors / therapeutic use
Immunogenic Cell Death / drug effects*
Neoplasms / drug therapy*
Neoplasms / immunology
Neoplasms / pathology
Peptides / pharmacology*
Peptides / therapeutic use
T-Lymphocytes, Cytotoxic / drug effects
T-Lymphocytes, Cytotoxic / immunology

Substances

Antigens, Neoplasm
Immune Checkpoint Inhibitors
Peptides