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Exploring Therapeutic Targets in the Evolving Landscape of Cancer Immunotherapy
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Exploring Therapeutic Targets in the Evolving Landscape of Cancer Immunotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 2522

Special Issue Editor

Dr. Domenico Galati

E-Mail Website
Guest Editor
Hematology-Oncology and Stem Cell Transplantation Unit, Department of Hematology and Innovative Diagnostic, Istituto Nazionale Tumori-IRCCS-Fondazione “G. Pascale” Napoli, 80131 Napoli, Italy
Interests: dendritic cells; immunotherapy; gamma-delta T cells; cancer biomarkers; tumor immunology; cytometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer immunotherapy has truly revolutionized oncology treatment, significantly enhancing patient survival rates. Recent strides in this field explore cutting-edge approaches, including personalized vaccines, combination therapies and advancements in CAR-T cell therapy, all aimed at elevating treatment specificity and the overall effectiveness. Researchers are deeply engaged in unraveling the complexities of the tumor microenvironment, with a focus on modulating immunosuppressive factors and augmenting T-cell infiltration for optimal treatment outcomes. These advancements underscore a nuanced understanding of immune systnem dynamics within the context of cancer, paving the way for more sophisticated and impactful therapeutic strategies.

This Special Issue is dedicated to the exploration of cancer immunotherapy, with a specific focus on immune targets, CAR- and TCR-engineered T cell therapy for both blood and solid cancers, as well as malignancies associated with viral infections. It spans dynamic areas of research, including DC-based immunotherapy, Treg cell-mediated immunosuppression and innate immune signaling, offering a collection of innovative ideas aimed at not only enhancing therapeutic efficacy, but also broadening the application of immunotherapy for a diverse range of cancer patients.

Dr. Domenico Galati
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • immune checkpoints
  • targeted therapies
  • tumor microenvironment
  • cancer immunology
  • precision medicine
  • cell-based cancer therapy

Published Papers (3 papers)

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Research

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10 pages, 845 KiB  
Communication
Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with Digital Droplet Polymerase Chain Reaction (ddPCR)
by Eugenio Galli, Marcello Viscovo, Federica Fosso, Ilaria Pansini, Giacomo Di Cesare, Camilla Iacovelli, Elena Maiolo, Federica Sorà, Stefan Hohaus, Simona Sica, Silvia Bellesi and Patrizia Chiusolo
Int. J. Mol. Sci. 2024, 25(5), 2673; https://doi.org/10.3390/ijms25052673 - 26 Feb 2024
Viewed by 736
Abstract
Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with [...] Read more.
Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A significant correlation between CAR-T counts determined by FCM and CAR transcripts assessed by ddPCR (p < 0.001) was observed. FCM revealed median CD3+CAR+ cell counts at 7, 14, and 30 days post-infusion with no significant differences. In contrast, ddPCR-measured median copies of CAR-T transcripts demonstrated significant lower copy numbers in tisa-cel recipients compared to the other products at day 7 and day 14. Patients with a peak of CAR transcripts at day 7 exceeding 5000 copies/microg gDNA, termed “good CAR-T expanders”, were more likely to achieve a favorable response at 3 months (HR 10.79, 95% CI 1.16–100.42, p = 0.036). Good CAR-T expanders showed superior progression-free survival at 3, 6, and 12 months compared to poor CAR-T expanders (p = 0.088). Those reaching a peak higher than 5000 copies/microg gDNA were more likely to experience severe CRS and ICANS. DdPCR proves to be a practical method for monitoring CAR-T expansion, providing quantitative information that better predicts both treatment outcomes and toxicity. Full article
(This article belongs to the Special Issue Exploring Therapeutic Targets in the Evolving Landscape of Cancer Immunotherapy)
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22 pages, 5015 KiB  
Article
Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis
by Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Matsuda, Ryosuke Maeoka, Fumihiko Nishimura, Mitsutoshi Nakamura, Shuichi Yamada, Young-Soo Park, Takahiro Tsujimura and Ichiro Nakagawa
Int. J. Mol. Sci. 2024, 25(4), 2435; https://doi.org/10.3390/ijms25042435 - 19 Feb 2024
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Abstract
Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and [...] Read more.
Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM. Full article
(This article belongs to the Special Issue Exploring Therapeutic Targets in the Evolving Landscape of Cancer Immunotherapy)
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Review

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21 pages, 3652 KiB  
Review
Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy
by Dharambir Kashyap and Huda Salman
Int. J. Mol. Sci. 2024, 25(7), 3780; https://doi.org/10.3390/ijms25073780 - 28 Mar 2024
Viewed by 619
Abstract
Breast cancer (BCA) remains the leading cause of cancer-related mortality among women worldwide. This review delves into the therapeutic challenges of BCA, emphasizing the roles of interleukin-13 receptor α2 (IL-13Rα2) and erythropoietin-producing hepatocellular receptor A2 (EphA2) in tumor progression and resistance. Highlighting their [...] Read more.
Breast cancer (BCA) remains the leading cause of cancer-related mortality among women worldwide. This review delves into the therapeutic challenges of BCA, emphasizing the roles of interleukin-13 receptor α2 (IL-13Rα2) and erythropoietin-producing hepatocellular receptor A2 (EphA2) in tumor progression and resistance. Highlighting their overexpression in BCA, particularly in aggressive subtypes, such as Her-2-enriched and triple-negative breast cancer (TNBC), we discuss the potential of these receptors as targets for chimeric antigen receptor T-cell (CAR-T) therapies. We examine the structural and functional roles of IL-13Rα2 and EphA2, their pathological significance in BCA, and the promising therapeutic avenues their targeting presents. With an in-depth analysis of current immunotherapeutic strategies, including the limitations of existing treatments and the potential of dual antigen-targeting CAR T-cell therapies, this review aims to summarize potential future novel, more effective therapeutic interventions for BCA. Through a thorough examination of preclinical and clinical studies, it underlines the urgent need for targeted therapies in combating the high mortality rates associated with Her-2-enriched and TNBC subtypes and discusses the potential role of IL-13Rα2 and EphA2 as promising candidates for the development of CAR T-cell therapies. Full article
(This article belongs to the Special Issue Exploring Therapeutic Targets in the Evolving Landscape of Cancer Immunotherapy)
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