Biotechnological Approaches and Tools for the Development of Cancer Immunotherapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 14421

Special Issue Editors


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Guest Editor
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II Via S. Pansini, 5 I-80131 Napoli, Italy
CEINGE Biotecnologie Avanzate S.C.aR.L., Via G. Salvatore 486, I-80145 Napoli, Italy
Interests: Molecular biology; biotechnology; cancer; cancer biology; oncolytic virus; HSV-1; immunotherapy; antibody screening; hypoxia; animal models

E-Mail Website
Guest Editor
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II Via S. Pansini, 5 I-80131 Napoli, Italy
CEINGE Biotecnologie Avanzate S.C.aR.L., Via G. Salvatore 486, I-80145 Napoli, Italy
Interests: Biochemistry; antibodies; fusion proteins; immunoconjugates; bi-specific antibodies; phage display; immunobiotechnology; cancer immunotherapy; cardioncology; signal transduction
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Special Issue Information

Dear Colleagues,

With the growing medical demands of contrasting emerging diseases and cancer, medical biotechnology provides a plethora of innovative systems and strategies, with significant potential for rapid application to both therapeutic and diagnostic demands. The consolidated field of cancer immunotherapy is keeping its promises, in terms of its potential to cure previously untreatable tumors, and it is amenable to further challenging advances. Accordingly, future developments are expected in both basic research acquisitions and in the rapid translation of knowledge to exploitable results, aiming at the development of novel goods and services for cancer immunotherapy.

To face these challenges, the Special Issue “Biotechnological approaches and tools for the development of cancer immunotherapeutics” aims to attract leading-edge research in cancer immunotherapy, making use of both consolidated and innovative biotechnological tools and strategies with potential to impact on the immunotherapy of tumors.

This Special Issue of Cancers, therefore, will encompass new research articles and timely reviews on all aspects of basic and applied biotechnological research to increase the exploitable knowledge in cancer immunotherapy.

Prof. Nicola Zambrano
Prof. Claudia De Lorenzo
Guest Editors

Manuscript Submission Information

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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.

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Keywords

  • medical biotechnology
  • immunotherapy
  • monoclonal antibody
  • immunoconjugates
  • bi-specific antibodies
  • tyrosine kinase inhibitors
  • checkpoint inhibitors
  • immune modulation
  • oncolytic virus
  • cancer vaccine
  • CAR T-cells
  • chimeric antigen receptor T-cell therapies
  • preclinical models
  • nucleic acid aptamers
  • compound screening technologies
  • phage display
  • ribosome display
  • drug selection methodologies

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Published Papers (3 papers)

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Research

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20 pages, 4493 KiB  
Article
Immunomodulatory mAbs as Tools to Investigate on Cis-Interaction of PD-1/PD-L1 on Tumor Cells and to Set Up Methods for Early Screening of Safe and Potent Combinatorial Treatments
by Cinzia Vetrei, Margherita Passariello, Guendalina Froechlich, Rosa Rapuano Lembo, Nicola Zambrano and Claudia De Lorenzo
Cancers 2021, 13(12), 2858; https://doi.org/10.3390/cancers13122858 - 8 Jun 2021
Cited by 12 | Viewed by 2976
Abstract
Antibodies targeting Immune Checkpoints (IC) on tumor infiltrating lymphocytes improve immune responses against cancer. Recently, the expression of some ICs has also been reported on cancer cells. We used the clinically validated Ipilimumab and Nivolumab and other novel human antibodies targeting Cytotoxic T- [...] Read more.
Antibodies targeting Immune Checkpoints (IC) on tumor infiltrating lymphocytes improve immune responses against cancer. Recently, the expression of some ICs has also been reported on cancer cells. We used the clinically validated Ipilimumab and Nivolumab and other novel human antibodies targeting Cytotoxic T- lymphocyte-antigen 4 (CTLA-4), Programmed Death receptor-1 (PD-1) and Programmed Death Ligand 1 (PD-L1) to shed light on the functions of these ICs in cancer cells. We show here for the first time that all these antagonistic mAbs are able to reduce Erk phosphorylation and, unexpectedly, to induce a significant increase of ICs expression on tumor cells, involving a hyperphosphorylation of NF-kB. On the contrary, agonistic PD-L1 and PD-1 recombinant proteins showed opposite effects by leading to a significant reduction of PD-1 and PD-L1, thus also suggesting the existence of a crosstalk in tumor cells between multiple ICs. Since the immunomodulatory mAbs show their higher anti-tumor efficacy by activating lymphocytes against cancer cells, we also investigated whether it was possible to identify the most efficient combinations of immunomodulatory mAbs for achieving potent anti-tumor efficacy associated with the lowest adverse side effects by setting up novel simple and predictive in vitro models based on co-cultures of tumor cells or human fetal cardiomyocytes with lymphocytes. We demonstrate here that novel combinations of immunomodulatory mAbs with more potent anti-cancer activity than Ipilimumab and Nivolumab combination can be identified with no or lower cardiotoxic side effects. Thus, we propose these co-cultures-based assays as useful tools to test also other combinatorial treatments of emerging immunomodulatory mAbs against different ICs for the early screening of most potent and safe combinatorial therapeutic regimens. Full article
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Review

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19 pages, 2414 KiB  
Review
Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies
by Marco Campisi, Sarah E. Shelton, Minyue Chen, Roger D. Kamm, David A. Barbie and Erik H. Knelson
Cancers 2022, 14(15), 3561; https://doi.org/10.3390/cancers14153561 - 22 Jul 2022
Cited by 10 | Viewed by 4222
Abstract
Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and [...] Read more.
Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and exhaustion and the presence of vascular barriers. Testing next-generation immune therapies remains challenging in animals, motivating sophisticated ex vivo models of human tumor biology and prognostic assays to predict treatment response in real-time while comprehensively recapitulating the human tumor immune microenvironment (TIME). This review examines current strategies for testing cell-based cancer immunotherapies using ex vivo microphysiological systems and microfluidic technologies. Insights into the multicellular interactions of the TIME will identify novel therapeutic strategies to help patients whose tumors are refractory or resistant to current immunotherapies. Altogether, these microphysiological systems (MPS) have the capability to predict therapeutic vulnerabilities and biological barriers while studying immune cell infiltration and killing in a more physiologically relevant context, thereby providing important insights into fundamental biologic mechanisms to expand our understanding of and treatments for currently incurable malignancies. Full article
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24 pages, 2870 KiB  
Review
High-Throughput Monoclonal Antibody Discovery from Phage Libraries: Challenging the Current Preclinical Pipeline to Keep the Pace with the Increasing mAb Demand
by Nicola Zambrano, Guendalina Froechlich, Dejan Lazarevic, Margherita Passariello, Alfredo Nicosia, Claudia De Lorenzo, Marco J. Morelli and Emanuele Sasso
Cancers 2022, 14(5), 1325; https://doi.org/10.3390/cancers14051325 - 4 Mar 2022
Cited by 19 | Viewed by 6283
Abstract
Monoclonal antibodies are among the most powerful therapeutics in modern medicine. Since the approval of the first therapeutic antibody in 1986, monoclonal antibodies keep holding great expectations for application in a range of clinical indications, highlighting the need to provide timely and sustainable [...] Read more.
Monoclonal antibodies are among the most powerful therapeutics in modern medicine. Since the approval of the first therapeutic antibody in 1986, monoclonal antibodies keep holding great expectations for application in a range of clinical indications, highlighting the need to provide timely and sustainable access to powerful screening options. However, their application in the past has been limited by time-consuming and expensive steps of discovery and production. The screening of antibody repertoires is a laborious step; however, the implementation of next-generation sequencing-guided screening of single-chain antibody fragments has now largely overcome this issue. This review provides a detailed overview of the current strategies for the identification of monoclonal antibodies from phage display-based libraries. We also discuss the challenges and the possible solutions to improve the limiting selection and screening steps, in order to keep pace with the increasing demand for monoclonal antibodies. Full article
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