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Cancers
Special Issues
The Use of Targeted Cytokine for Novel Cancer Therapeutics
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The Use of Targeted Cytokine for Novel Cancer Therapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 9500

Special Issue Editors

Prof. Dr. Leonidas C Platanias

E-Mail Website
Guest Editor
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA
Interests: interferon; leukemia; immunotherapy; cytokines; signaling
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Amy Heimberger

E-Mail Website
Guest Editor
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA
Interests: immunotherapy; glioblastoma; tumor microenvironment; signal transducer and activator of transcription 3 (STAT3); cGAS-STING cytosolic DNA sensing; translational therapeutics

Special Issue Information

Dear Colleagues, 

This Special Issue will address the evolving role of immune modulatory cytokines from their initial use as monotherapeutic recombinant proteins to their more contemporaneous use, for example as modifiers for adoptive T cell immunotherapy. Sustained delivery platforms, such as viral therapy and self-replicating mRNA strategies delivered into the tumor microenvironment, may provide more reasonable clinical delivery schedules while minimizing systemic toxicities. The discovery of new cytokines that are at the convergence of both immune modulation and tumorigenesis will likely serve as the next generation of cytokine therapeutics. Approaches aimed to target cytokine inducible genes and their protein products will be also discussed.

Prof. Dr. Leonidas C Platanias
Prof. Dr. Amy Heimberger
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

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Editorial

Jump to: Review

9 pages, 1714 KiB  
Editorial
Targeting Cytokines and Their Pathways for the Treatment of Cancer
by Amy B. Heimberger, Shashwat Tripathi and Leonidas C. Platanias
Cancers 2023, 15(21), 5224; https://doi.org/10.3390/cancers15215224 - 30 Oct 2023
Cited by 4 | Viewed by 1819
Abstract
This Special Issue focuses on the evolving role of immune modulatory cytokines, from their initial use as monotherapeutic recombinant proteins to their more contemporaneous use as modifiers for adoptive cellular immunotherapy [...] Full article
(This article belongs to the Special Issue The Use of Targeted Cytokine for Novel Cancer Therapeutics)
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Review

Jump to: Editorial

16 pages, 788 KiB  
Review
Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma
by Kristen D. Pawlowski, Joseph T. Duffy, Stephen Gottschalk and Irina V. Balyasnikova
Cancers 2023, 15(24), 5852; https://doi.org/10.3390/cancers15245852 - 15 Dec 2023
Cited by 3 | Viewed by 2244
Abstract
Chimeric antigen receptor (CAR) cell-based therapies have demonstrated limited success in solid tumors, including glioblastoma (GBM). GBMs exhibit high heterogeneity and create an immunosuppressive tumor microenvironment (TME). In addition, other challenges exist for CAR therapy, including trafficking and infiltration into the tumor site, [...] Read more.
Chimeric antigen receptor (CAR) cell-based therapies have demonstrated limited success in solid tumors, including glioblastoma (GBM). GBMs exhibit high heterogeneity and create an immunosuppressive tumor microenvironment (TME). In addition, other challenges exist for CAR therapy, including trafficking and infiltration into the tumor site, proliferation, persistence of CARs once in the tumor, and reduced functionality, such as suboptimal cytokine production. Cytokine modification is of interest, as one can enhance therapy efficacy and minimize off-target toxicity by directly combining CAR therapy with cytokines, antibodies, or oncolytic viruses that alter cytokine response pathways. Alternatively, one can genetically modify CAR T-cells or CAR NK-cells to secrete cytokines or express cytokines or cytokine receptors. Finally, CARs can be genetically altered to augment or suppress intracellular cytokine signaling pathways for a more direct approach. Codelivery of cytokines with CARs is the most straightforward method, but it has associated toxicity. Alternatively, combining CAR therapy with antibodies (e.g., anti-IL-6, anti-PD1, and anti-VEGF) or oncolytic viruses has enhanced CAR cell infiltration into GBM tumors and provided proinflammatory signals to the TME. CAR T- or NK-cells secreting cytokines (e.g., IL-12, IL-15, and IL-18) have shown improved efficacy within multiple GBM subtypes. Likewise, expressing cytokine-modulating receptors in CAR cells that promote or inhibit cytokine signaling has enhanced their activity. Finally, gene editing approaches are actively being pursued to directly influence immune signaling pathways in CAR cells. In this review, we summarize these cytokine modification methods and highlight any existing gaps in the hope of catalyzing an improved generation of CAR-based therapies for glioblastoma. Full article
(This article belongs to the Special Issue The Use of Targeted Cytokine for Novel Cancer Therapeutics)
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17 pages, 1034 KiB  
Review
The Use of Targeted Cytokines as Cancer Therapeutics in Glioblastoma
by Moloud Sooreshjani, Shashwat Tripathi, Corey Dussold, Hinda Najem, John de Groot, Rimas V. Lukas and Amy B. Heimberger
Cancers 2023, 15(14), 3739; https://doi.org/10.3390/cancers15143739 - 23 Jul 2023
Cited by 2 | Viewed by 2460
Abstract
Cytokines play an important role in regulating the immune response. Although there is great interest in exploiting cytokines for cancer immunotherapy, their clinical potential is limited by their pleiotropic properties and instability. A variety of cancer cell-intrinsic and extrinsic characteristics pose a barrier [...] Read more.
Cytokines play an important role in regulating the immune response. Although there is great interest in exploiting cytokines for cancer immunotherapy, their clinical potential is limited by their pleiotropic properties and instability. A variety of cancer cell-intrinsic and extrinsic characteristics pose a barrier to effective treatments including cytokines. Recent studies using gene and cell therapy offer new opportunities for targeting cytokines or their receptors, demonstrating that they are actionable targets. Current efforts such as virotherapy, systemic cytokine therapy, and cellular and gene therapy have provided novel strategies that incorporate cytokines as potential therapeutic strategies for glioblastoma. Ongoing research on characterizing the tumor microenvironment will be informative for prioritization and combinatorial strategies of cytokines for future clinical trials. Unique therapeutic opportunities exist at the convergence of cytokines that play a dual role in tumorigenesis and immune modulation. Here, we discuss the underlying strategies in pre- and clinical trials aiming to enhance treatment outcomes in glioblastoma patients. Full article
(This article belongs to the Special Issue The Use of Targeted Cytokine for Novel Cancer Therapeutics)
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17 pages, 1652 KiB  
Review
Immunobiology and Cytokine Modulation of the Pediatric Brain Tumor Microenvironment: A Scoping Review
by Shreya Budhiraja, Hinda Najem, Shashwat Tripathi, Nitin R. Wadhawani, Craig Horbinski, Matthew McCord, Alicia C. Lenzen, Amy B. Heimberger and Michael DeCuypere
Cancers 2023, 15(14), 3655; https://doi.org/10.3390/cancers15143655 - 18 Jul 2023
Cited by 1 | Viewed by 1835
Abstract
Utilizing a Scoping Review strategy in the domain of immune biology to identify immune therapeutic targets, knowledge gaps for implementing immune therapeutic strategies for pediatric brain tumors was assessed. The analysis demonstrated limited efforts to date to characterize and understand the immunological aspects [...] Read more.
Utilizing a Scoping Review strategy in the domain of immune biology to identify immune therapeutic targets, knowledge gaps for implementing immune therapeutic strategies for pediatric brain tumors was assessed. The analysis demonstrated limited efforts to date to characterize and understand the immunological aspects of tumor biology with an over-reliance on observations from the adult glioma population. Foundational knowledge regarding the frequency and ubiquity of immune therapeutic targets is an area of unmet need along with the development of immune-competent pediatric tumor models to test therapeutics and especially combinatorial treatment. Opportunities arise in the evolution of pediatric tumor classification from histological to molecular with targeted immune therapeutics. Full article
(This article belongs to the Special Issue The Use of Targeted Cytokine for Novel Cancer Therapeutics)
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