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Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design

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: closed (31 May 2022) | Viewed by 21055

Special Issue Editors

Prof. Dr. Michael P. Bachmann

E-Mail Website
Guest Editor
Helmholtz Zentrum Dresden Rossendorf, Institute of Radio­pharma­ceutical Cancer Research, Bautzner Landstr 400, D-01328 Dresden, Germany
Interests: (radio)immunotherapy and imaging of tumors; bispecific antibodies; genetically modified immune effector cells; autoimmunity
Special Issues, Collections and Topics in MDPI journals
Dr. Anja Feldmann

E-Mail Website
Guest Editor
Department Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz Zentrum Dresden Rossendorf (HZDR), 01328 Dresden, Germany
Interests: chimeric antigen receptors; B cell maturation antigen; biological therapy; antibody engineering; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Within the last few decades, immunotherapy has gained an increasingly important role beyond standard therapies and is thus considered as the forth pillar of anti-cancer therapy. However, from a clinical perspective, not only an efficient treatment but also reasonable patient selection and therapy monitoring are highly required for improved patient outcomes. Recent advances in immunotheranostics can pave the way towards precision oncology and personalized medicine. The implementation of imaging tools before, during, or after immunotherapy, especially in the case of living drugs, can help predict and understand possible effects, as well as side effects of immunotherapy. Further, they can prospectively allow therapeutic interventions if needed. Precise and periodic target verification and assessment of molecular response to therapy can help decision-making and guide appropriate patient-specific treatment.

This Special Issue aims to provide a comprehensive overview of recent advances in cancer immunotheranostics and their significance for personalized medicine. Basic and translational original or review articles submitted to this issue may address various types of immunotherapeutics ranging from small molecules, peptides, nanoparticles, nanobodies, full-size, and recombinant antibodies to cells. Authors are encouraged to address topics including but not limited to biomedical research in the field of theranostic development, target and biomarker identification, novel targeted immunotheranostics, molecular in vivo imaging, or sophisticated combinatorial approaches for immunotherapy and tumor visualization.

Prof. Michael P. Bachmann
Dr. Anja Feldmann
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. 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

  • Immunotheranostics
  • Molecular Imaging
  • Radioimmunotherapy
  • Cancer Immunotherapy
  • Targeted Therapy
  • Biochemical Response
  • Image-guided Therapy
  • Drug Development

Related Special Issue

Published Papers (6 papers)

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Research

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16 pages, 2453 KiB  
Article
Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells
by Diana Lindner, Claudia Arndt, Liliana Rodrigues Loureiro, Anja Feldmann, Alexandra Kegler, Stefanie Koristka, Nicole Berndt, Nicola Mitwasi, Ralf Bergmann, Marcus Frenz and Michael P. Bachmann
Int. J. Mol. Sci. 2022, 23(14), 7922; https://doi.org/10.3390/ijms23147922 - 18 Jul 2022
Cited by 2 | Viewed by 2229
Abstract
Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors [...] Read more.
Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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13 pages, 4457 KiB  
Article
A MLR-Based Approach to Analyze Regulators of T Lymphocyte Activation In Vivo
by Jiří Koutník, Victoria Klepsch, Maria Pommermayr, Nikolaus Thuille, Gottfried Baier and Kerstin Siegmund
Int. J. Mol. Sci. 2022, 23(10), 5337; https://doi.org/10.3390/ijms23105337 - 10 May 2022
Cited by 2 | Viewed by 2135
Abstract
Depending on the context, robust and durable T lymphocyte activation is either desirable, as in the case of anti-tumor responses, or unwanted, in cases of autoimmunity when chronic stimulation leads to self-tissue damage. Therefore, reliable in vivo models are of great importance to [...] Read more.
Depending on the context, robust and durable T lymphocyte activation is either desirable, as in the case of anti-tumor responses, or unwanted, in cases of autoimmunity when chronic stimulation leads to self-tissue damage. Therefore, reliable in vivo models are of great importance to identify and validate regulatory pathways of T lymphocyte activation. Here, we describe an in vivo mixed-lymphocyte-reaction (MLR) approach, which is based on the so-called parent-into-F1 (P → F1) mouse model in combination with the congenic marker CD45.1/2 and cell proliferation dye-labeling. This setup allows us to track adoptively transferred allogenic CD4+ and CD8+ T lymphocytes and analyze their phenotype as well as the proliferation by flow cytometry in the blood and spleen. We could show hypo-reactive responses of T lymphocytes isolated from knockout mice with a known defect in T lymphocyte activation. Thus, this MLR-based in vivo model provides the opportunity to analyze positive regulators of T cell responses under physiological conditions of polyclonal T lymphocyte activation in vivo. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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14 pages, 2239 KiB  
Article
Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)
by Nicola Mitwasi, Claudia Arndt, Liliana R. Loureiro, Alexandra Kegler, Frederick Fasslrinner, Nicole Berndt, Ralf Bergmann, Vaclav Hořejší, Claudia Rössig, Michael Bachmann and Anja Feldmann
Int. J. Mol. Sci. 2022, 23(9), 4920; https://doi.org/10.3390/ijms23094920 - 28 Apr 2022
Cited by 3 | Viewed by 2695
Abstract
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), [...] Read more.
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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16 pages, 3786 KiB  
Article
Targeted Delivery of Immunostimulatory CpG Oligodeoxynucleotides to Antigen-Presenting Cells in Draining Lymph Nodes by Stearic Acid Modification and Nanostructurization
by Makoto Nagaoka, Wenqing Liao, Kosuke Kusamori and Makiya Nishikawa
Int. J. Mol. Sci. 2022, 23(3), 1350; https://doi.org/10.3390/ijms23031350 - 25 Jan 2022
Cited by 2 | Viewed by 2220
Abstract
Polypod-like structured nucleic acids (polypodnas), which are nanostructured DNAs, are useful for delivering cytosine-phosphate guanine oligodeoxynucleotides (CpG ODNs) to antigen-presenting cells (APCs) expressing Toll-like receptor 9 (TLR9) for immune stimulation. Lipid modification is another approach to deliver ODNs to lymph nodes, where TLR9-positive [...] Read more.
Polypod-like structured nucleic acids (polypodnas), which are nanostructured DNAs, are useful for delivering cytosine-phosphate guanine oligodeoxynucleotides (CpG ODNs) to antigen-presenting cells (APCs) expressing Toll-like receptor 9 (TLR9) for immune stimulation. Lipid modification is another approach to deliver ODNs to lymph nodes, where TLR9-positive APCs are abundant, by binding to serum albumin. The combination of these two methods can be useful for delivering CpG ODNs to lymph nodes in vivo. In the present study, CpG1668, a phosphodiester-type CpG ODN, was modified with stearic acid (SA) to obtain SA-CpG1668. Tripodna, a polypodna with three pods, was selected as the nanostructured DNA. Tripodnas loaded with CpG1668 or SA-CpG1668 were obtained in high yields. SA-CpG1668/tripodna bound more efficiently to plasma proteins than CpG1668/tripodna and was more efficiently taken up by macrophage-like RAW264.7 cells than CpG1668/tripodna, whereas the levels of tumor necrosis factor-α released from the cells were comparable between the two. After subcutaneous injection into mice, SA-CpG1668/tripodna induced significantly higher interleukin (IL)-12 p40 production in the draining lymph nodes than SA-CpG1668 or CpG1668/tripodna, with reduced IL-6 levels in plasma. These results indicate that the combination of SA modification and nanostructurization is a useful approach for the targeted delivery of CpG ODNs to lymph nodes. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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Review

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17 pages, 2038 KiB  
Review
Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy
by Masahiro Okada, Kanako Shimizu and Shin-ichiro Fujii
Int. J. Mol. Sci. 2022, 23(5), 2594; https://doi.org/10.3390/ijms23052594 - 26 Feb 2022
Cited by 15 | Viewed by 6049
Abstract
The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor [...] Read more.
The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors. Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy. Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies. However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens. We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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27 pages, 1409 KiB  
Review
Challenges and Recent Advances in NK Cell-Targeted Immunotherapies in Solid Tumors
by Guangyu Lian, Thomas Shiu-Kwong Mak, Xueqing Yu and Hui-Yao Lan
Int. J. Mol. Sci. 2022, 23(1), 164; https://doi.org/10.3390/ijms23010164 - 23 Dec 2021
Cited by 13 | Viewed by 4813
Abstract
Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies [...] Read more.
Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies achieved great success in clinical trials against hematologic malignancies, their accumulation, activation, cytotoxic and immunoregulatory functions are severely impaired in the immunosuppressive microenvironment of solid tumors. Now with better understandings of the tumor evasive mechanisms from NK-mediated immunosurveillance, immunotherapies targeting the key molecules for NK cell dysfunction and exhaustion have been developed and tested in both preclinical and clinical studies. In this review, we introduce the challenges that NK cells encountered in solid tumor microenvironment (TME) and the therapeutic approaches to overcome these limitations, followed by an outline of the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies, as well as promising strategies to optimize current NK-targeted immunotherapies for solid tumors. Full article
(This article belongs to the Special Issue Recent Advances in Immunotheragnostics: From Molecular Basis to Targeted Pharmaceutical Design)
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