Targeted Treatment for Immunochemotherapy in Cancer

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 December 2022) | Viewed by 18561

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Immunological and Oncological Center Cologne (IOZK), Koln, Germany
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Dear Colleagues

Although the “war against cancer” has been going on for many years already, the road toward improvement of the prognosis of cancer patients remains incredibly challenging. However, new insights gained over the last few years might offer a glimpse of hope. Indeed, new pillars in addition to surgery, radiotherapy, and chemotherapy are being developed, among them targeted therapies, immunotherapies (restorative, modulatory, passive, or active specific immunotherapy), biological treatments such as oncolytic viruses, and physics-based treatments such as nanomaterials, electromagnetic waves, etc. Most importantly, however, the host in which the cancer exists is now recognized as playing a crucial role. Therefore, research is increasingly focusing on the tumor micro-environment. Concepts such as immunogenic cell death are elaborated in different treatment domains: killing the tumor cell and thereby stimulating the immune system in order to amplify the anticancer effect and prolong tumor control via the immune activation.

Already in 2013, cancer immunotherapy was recognized as the breakthrough of the year. A lot of cell-based treatment technologies are under development and being applied in clinics. Along these developments, terms such as “biology-driven treatments” and “personalized treatments” are often dominant. Although personalized, some immunotherapies are considered “agnostic therapies”, as they are no longer linked to specific tumor entities. Finally, the term “combination treatment” seems to reflect the future of the field.

Novel strategies represent huge challenges for running classical randomized controlled clinical trials, as these should not only be stratified on tumor-related characteristics, but also on micro-environment- and patient-related characteristics. The high number of new approaches available force innovation in healthcare organization. Classical concepts of evidence-based medicine need to be supplemented with strong science-based treatment concepts implemented in translational medicine and fully supported by national health systems.

We therefore invite colleagues to submit their contributions in the topic to this Special Issue.

Dr. Stefaan Willy van Gool
Guest Editor

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Keywords

  • targeted therapy
  • immunotherapy
  • immunogenic cell death
  • biology-driven treatment
  • personalized medicine
  • agnostic therapy

Published Papers (4 papers)

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Research

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17 pages, 3888 KiB  
Article
In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models
by Massis Krekorian, Kimberley R. G. Cortenbach, Milou Boswinkel, Annemarie Kip, Gerben M. Franssen, Andor Veltien, Tom W. J. Scheenen, René Raavé, Nicolaas Koen van Riessen, Mangala Srinivas, Ingrid Jolanda M. de Vries, Carl G. Figdor, Erik H. J. G. Aarntzen and Sandra Heskamp
Cancers 2021, 13(20), 5069; https://doi.org/10.3390/cancers13205069 - 10 Oct 2021
Cited by 4 | Viewed by 2450
Abstract
The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. 111In-labeled poly(lactic-co-glycolic acid) with a primary [...] Read more.
The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. 111In-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([111In]In-PLGA-NH2 NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed 89Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH2 NPs with [89Zr]ZrCl4. In vitro, [89Zr]Zr-PLGA-NH2 NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 ± 10 kBq/106 cells). PET/MRI imaging could detect low numbers of [89Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [89Zr]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular Staphylococcus aureus infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [89Zr]Zr-PLGA-NH2 NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models. Full article
(This article belongs to the Special Issue Targeted Treatment for Immunochemotherapy in Cancer)
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Review

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35 pages, 996 KiB  
Review
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
by Iñigo Les, Mireia Martínez, Inés Pérez-Francisco, María Cabero, Lucía Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Iñaki Elejalde, Grazyna Kochan and David Escors
Cancers 2023, 15(5), 1629; https://doi.org/10.3390/cancers15051629 - 6 Mar 2023
Cited by 11 | Viewed by 5641
Abstract
Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell [...] Read more.
Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site. Full article
(This article belongs to the Special Issue Targeted Treatment for Immunochemotherapy in Cancer)
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20 pages, 749 KiB  
Review
Immunotherapy in Medulloblastoma: Current State of Research, Challenges, and Future Perspectives
by Marije J. Voskamp, Shuang Li, Kim R. van Daalen, Sandra Crnko, Toine ten Broeke and Niels Bovenschen
Cancers 2021, 13(21), 5387; https://doi.org/10.3390/cancers13215387 - 27 Oct 2021
Cited by 11 | Viewed by 4226
Abstract
Medulloblastoma (MB), a primary tumor of the central nervous system, is among the most prevalent pediatric neoplasms. The median age of diagnosis is six. Conventional therapies include surgical resection of the tumor with subsequent radiation and chemotherapy. However, these therapies often cause severe [...] Read more.
Medulloblastoma (MB), a primary tumor of the central nervous system, is among the most prevalent pediatric neoplasms. The median age of diagnosis is six. Conventional therapies include surgical resection of the tumor with subsequent radiation and chemotherapy. However, these therapies often cause severe brain damage, and still, approximately 75% of pediatric patients relapse within a few years. Because the conventional therapies cause such severe damage, especially in the pediatric developing brain, there is an urgent need for better treatment strategies such as immunotherapy, which over the years has gained accumulating interest. Cancer immunotherapy aims to enhance the body’s own immune response to tumors and is already widely used in the clinic, e.g., in the treatment of melanoma and lung cancer. However, little is known about the possible application of immunotherapy in brain cancer. In this review, we will provide an overview of the current consensus on MB classification and the state of in vitro, in vivo, and clinical research concerning immunotherapy in MB. Based on existing evidence, we will especially focus on immune checkpoint inhibition and CAR T-cell therapy. Additionally, we will discuss challenges associated with these immunotherapies and relevant strategies to overcome those. Full article
(This article belongs to the Special Issue Targeted Treatment for Immunochemotherapy in Cancer)
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26 pages, 2601 KiB  
Review
The Current Landscape of NKT Cell Immunotherapy and the Hills Ahead
by Adam Nelson, Jordan D. Lukacs and Brent Johnston
Cancers 2021, 13(20), 5174; https://doi.org/10.3390/cancers13205174 - 15 Oct 2021
Cited by 48 | Viewed by 5236
Abstract
NKT cells are a specialized subset of lipid-reactive T lymphocytes that play direct and indirect roles in immunosurveillance and anti-tumor immunity. Preclinical studies have shown that NKT cell activation via delivery of exogenous glycolipids elicits a significant anti-tumor immune response. Furthermore, infiltration of [...] Read more.
NKT cells are a specialized subset of lipid-reactive T lymphocytes that play direct and indirect roles in immunosurveillance and anti-tumor immunity. Preclinical studies have shown that NKT cell activation via delivery of exogenous glycolipids elicits a significant anti-tumor immune response. Furthermore, infiltration of NKT cells is associated with a good prognosis in several cancers. In this review, we aim to summarize the role of NKT cells in cancer as well as the current strategies and status of NKT cell immunotherapy. This review also examines challenges and future directions for improving the therapy. Full article
(This article belongs to the Special Issue Targeted Treatment for Immunochemotherapy in Cancer)
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