Cytokines in Clinical Cancer Immunotherapy

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

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 10496

Special Issue Editors

Department of Medicine, Moores Cancer Center & Sanford Stem Cell Clinical Center, University of California San Diego, La Jolla, CA, USA
Interests: cancer immunotherapy; tumor antigen; antigen presentation; tumor antigen-specific cytotoxic T lymphocytes (CTLs); tumor-infiltrating lymphocytes (TILs); tumor antigen delivery with nanotechnology; targeted cancer therapy; cancer stem cell (CSC); circulating tumor cell (CTC); biomarkers

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Co-Guest Editor
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale Cancer Center, Yale University, New Haven, CT, USA
Interests: immune checkpoints and cancer progression; immune escaping; immune responses; neoantigen presentation; T cell infiltration; microenvironmental factors; immune checkpoints; T cell activation; tumor progression; individualize immunotherapy
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Special Issue Information

Dear Colleagues, 

The application of immunotherapy in clinical practice has significantly benefited cancer patients, particularly those with advanced disease. However, not all patients respond to immunotherapy. In combination with other regimens (e.g., chemotherapy, targeted therapy, and radiotherapy), improvement in patient survival suggests that interactions among immune cells, cancer cells, and microenvironments exist. Obtaining a better understanding of the potential mechanisms underlying these interactions, identifying the factors that affect these interactions and the efficacy of immunotherapy, evaluating the efficacy of combinations of different regimens, and identifying predictive and prognostic markers may help us to design better strategies for use in treatment and clinical practice. Current cancer immunotherapies include immune checkpoint inhibitors (ICIs), adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), engineered T cell receptor therapy (TCR-T), CAR T cell therapy, and Natural Killer cell therapy), monoclonal antibodies, oncolytic virus therapy, cancer vaccines, and immune system modulators such as interleukins (IL) and interferons (IFN).

We are pleased to invite you to contribute to this special issue.

This Special Issue aims to publish not only reproduced experimental and theoretical results, but also meaningful but negative results so that other researchers do not need to repeat these experiments any longer within this scope. Both translational and clinical studies are welcome.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: immune checkpoint inhibitors (ICIs), adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), engineered T cell receptor therapy (TCR-T), monoclonal antibodies, and immune system modulators).

I look forward to receiving your contributions.

Dr. Wenxue Ma
Dr. Lingeng Lu
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 short 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.

Keywords

  • cancer Immunotherapy
  • immune checkpoint inhibitors (ICIs)
  • tumor-infiltrating lymphocytes (TILs)
  • engineered T cell receptor (TCR)
  • Chimeric Antigen Receptor (CAR) T cells
  • Natural Killer (NK) cells
  • monoclonal antibodies
  • cytokines
  • clinical trial
  • preclinical

Published Papers (4 papers)

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Research

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18 pages, 2044 KiB  
Article
Development of Allogeneic Stem Cell-Based Platform for Delivery and Potentiation of Oncolytic Virotherapy
by Duong Hoang Nguyen, Thomas Herrmann, Barbara Härtl, Dobrin Draganov, Ivelina Minev, Forrest Neuharth, Alberto Gomez, Ashley Alamillo, Laura Edith Schneider, Daniela Kleinholz, Boris Minev and Antonio F. Santidrian
Cancers 2022, 14(24), 6136; https://doi.org/10.3390/cancers14246136 - 13 Dec 2022
Cited by 1 | Viewed by 2111
Abstract
We describe the repurposing and optimization of the TK-positive (thymidine kinase) vaccinia virus strain ACAM1000/ACAM2000™ as an oncolytic virus. This virus strain has been widely used as a smallpox vaccine and was also used safely in our recent clinical trial in patients with [...] Read more.
We describe the repurposing and optimization of the TK-positive (thymidine kinase) vaccinia virus strain ACAM1000/ACAM2000™ as an oncolytic virus. This virus strain has been widely used as a smallpox vaccine and was also used safely in our recent clinical trial in patients with advanced solid tumors and Acute Myeloid Leukemia (AML). The vaccinia virus was amplified in CV1 cells and named CAL1. CAL1 induced remarkable oncolysis in various human and mouse cancer cells and preferentially amplified in cancer cells, supporting the use of this strain as an oncolytic virus. However, the therapeutic potential of CAL1, as demonstrated with other oncolytic viruses, is severely restricted by the patients’ immune system. Thus, to develop a clinically relevant oncolytic virotherapy agent, we generated a new off-the-shelf therapeutic called Supernova1 (SNV1) by loading CAL1 virus into allogeneic adipose-derived mesenchymal stem cells (AD-MSC). Culturing the CAL1-infected stem cells allows the expression of virally encoded proteins and viral amplification prior to cryopreservation. We found that the CAL1 virus loaded into AD-MSC was resistant to humoral inactivation. Importantly, the virus-loaded stem cells (SNV1) released larger number of infectious viral particles and virally encoded proteins, leading to augmented therapeutic efficacy in vitro and in animal tumor models. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
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Review

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20 pages, 765 KiB  
Review
How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles
by Yan Fu, Chu Hui Zeng, Chao An, Yue Liu, Ji Hoon Shin and Xiao Li
Cancers 2023, 15(4), 1324; https://doi.org/10.3390/cancers15041324 - 19 Feb 2023
Cited by 1 | Viewed by 1914
Abstract
As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on [...] Read more.
As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on treating HCC, but the efficacy of their individual application is limited. Therefore, the purpose of this review was to discuss the biological roles of cytokines and their therapeutic potential in the combination therapy of LITs and ICI-based immunotherapy. The two common techniques of LITs are ablative and transarterial therapies. Whether LITs are complete or incomplete can largely affect the antitumor immune response and tumor progression. Cytokines that induce both local and systemic responses to LITs, including interferons, interleukins, chemokines, TNF-α, TGF-β, VEGF, and HGF, and their roles are discussed in detail. In addition, specific cytokines that can be used as therapeutic targets to reduce immune-related adverse events (irAEs) are introduced. Overall, incomplete LITs in a tumor, combined with specific cytokines, are thought to be effective at improving the therapeutic efficacy and reducing treatment-induced irAEs, and represent a new hope for managing unresectable HCC. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
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30 pages, 1375 KiB  
Review
Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
by Qiuqiang Chen, Lingeng Lu and Wenxue Ma
Cancers 2022, 14(23), 5983; https://doi.org/10.3390/cancers14235983 - 3 Dec 2022
Cited by 7 | Viewed by 3277
Abstract
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy [...] Read more.
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
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14 pages, 1069 KiB  
Review
Antitumor Activities of Interleukin-12 in Melanoma
by Wei Gao, Jun Pan and Jianping Pan
Cancers 2022, 14(22), 5592; https://doi.org/10.3390/cancers14225592 - 14 Nov 2022
Cited by 5 | Viewed by 2009
Abstract
Melanoma is the most common and serious malignant tumor among skin cancers. Although more and more studies have revolutionized the systematic treatment of advanced melanoma in recent years, access to innovative drugs for melanoma is still greatly restricted in many countries. IL-12 produced [...] Read more.
Melanoma is the most common and serious malignant tumor among skin cancers. Although more and more studies have revolutionized the systematic treatment of advanced melanoma in recent years, access to innovative drugs for melanoma is still greatly restricted in many countries. IL-12 produced mainly by antigen-presenting cells regulates the immune response and affects the differentiation of T cells in the process of antigen presentation. However, the dose-limited toxicity of IL-12 limits its clinical application. The present review summarizes the basic biological functions and toxicity of IL-12 in the treatment of melanoma and discusses the clinical application of IL-12, especially the combination of IL-12 with immune checkpoint inhibitors, cytokines and other therapeutic drugs. We also summarize several promising technological approaches such as carriers that have been developed to improve the pharmacokinetics, efficacy and safety of IL-12 or IL-12 encoding plasmid application. Full article
(This article belongs to the Special Issue Cytokines in Clinical Cancer Immunotherapy)
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