Immunotherapy for Cancers

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 2028

Special Issue Editors


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Guest Editor
1. Laboratory of Immunology and General Pathology, University of Insubria, Varese, Italy
2. Laboratory of Innate Immunity, IRCCS MultiMedica, Milan, Italy
Interests: natural killer cells; innate lymphoid cells; tumor microenvironment; tumor angiogenesis; tumor immunology; immunotherapy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Laboratory of Innate Immunity, IRCCS MultiMedica, Milan, Italy
Interests: natural killer cells; neutrophils; myeloid-derived suppressor cells; T cells; tumor immunology; mesenchymal cells; ZEB1; angiogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer immunotherapy is a revolutionary tool to fight against cancer, restoring/re-awakening the immune host response by different approaches including vaccines (including nano-vaccines), cell therapies (including CAR-T and, more recently, CAR-NK), modified antibodies, immunocytokines, etc.

Although immunotherapy has emerged as the “next generation” of cancer treatment, it has not yet been shown to be successful in the treatment of all cancer types, for whom the preferential therapeutic options still remain radiotherapy, chemotherapy, and target therapy. This strongly suggests that a deeper examination of the interactions between immune cells in the micro- and macro-environment, which are currently poorly characterized, is still crucial for the clinical outcome and success of immunotherapy.

From this perspective, the immune-tumor microenvironment (TIME), as a key element in the new era of immunotherapy, has become a major challenge, and reverting this in the case of resistance to immunotherapy is still a major challenge. During this time, the roles of tissue-residing cells in promoting or suppressing tumor growth, metastasis and resistance to therapy have been gradually elucidated. Immunotherapy presents an opportunity to fight against cancer; several strategies have been employed but not all are successful. It is therefore clear that in the “window of unsuccessful immunotherapy”, a deeper knowledge of cellular and molecular mechanisms regulating immune suppression and angiogenesis is still required. It is also now clear that immunotherapy alone is not sufficient to eliminate cancer, thus opening new windows for therapeutic approaches based on combinations (in term of molecules and timing/sequences of their administration).

For this Special Issue, we aim to collect original research, reviews, mini-reviews and perspective articles reviewing/discussing the state of the art and/or proposing novel insights in basic and translational research of cancer immunotherapy. Areas of interest include but are not limited to:

  • High-throughput (“omics” and bioinformatic) approaches followed by experimental validation to dissect (novel) molecular targets for cancer immunotherapy;
  • TME/TIME-oriented molecular and cellular mechanisms/targets as potential candidates for immunotherapy;
  • The role of chronic inflammation and fibrosis in permitting immune-escape and/or resistance to immunotherapy;
  • Metabolic and immunometabolic drivers of immunosuppression, tumor progression/metastasis and resistance to cancer immunotherapy;
  • Combination approaches, including drug repurposing, in cancer immunotherapy;
  • Novel diagnostic or prognostic tools for cancer immunotherapy;
  • Stromal–immune cell interactions driving tumor progression, immunoescape and resistance to immunotherapy;
  • Epigenetics and immunotherapy;
  • Marine drugs and phytochemicals able to potentiate the immune response against cancers.

You may choose our Joint Special Issue in Cancers.

Dr. Antonino Bruno
Dr. Barbara Bassani
Guest Editors

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Keywords

  • cancer immunotherapy
  • innate immunity
  • adaptive immunity
  • tumor immune microenvironment
  • tumor microenvironment
  • combination therapies
  • drug repurposing

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Published Papers (1 paper)

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Research

21 pages, 5582 KiB  
Article
HER2-CD3-Fc Bispecific Antibody-Encoding mRNA Delivered by Lipid Nanoparticles Suppresses HER2-Positive Tumor Growth
by Liang Hu, Shiming Zhang, John Sienkiewicz, Hua Zhou, Robert Berahovich, Jinying Sun, Michael Li, Adrian Ocampo, Xianghong Liu, Yanwei Huang, Hizkia Harto, Shirley Xu, Vita Golubovskaya and Lijun Wu
Vaccines 2024, 12(7), 808; https://doi.org/10.3390/vaccines12070808 - 21 Jul 2024
Viewed by 1458
Abstract
The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter [...] Read more.
The human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor and tumor-associated antigen abnormally expressed in various types of cancer, including breast, ovarian, and gastric cancer. HER2 overexpression is highly correlated with increased tumor aggressiveness, poorer prognosis, and shorter overall survival. Consequently, multiple HER2-targeted therapies have been developed and approved; however, only a subset of patients benefit from these treatments, and relapses are common. More potent and durable HER2-targeted therapies are desperately needed for patients with HER2-positive cancers. In this study, we developed a lipid nanoparticle (LNP)-based therapy formulated with mRNA encoding a novel HER2-CD3-Fc bispecific antibody (bsAb) for HER2-positive cancers. The LNPs efficiently transfected various types of cells, such as HEK293S, SKOV-3, and A1847, leading to robust and sustained secretion of the HER2-CD3-Fc bsAb with high binding affinity to both HER2 and CD3. The bsAb induced potent T-cell-directed cytotoxicity, along with secretion of IFN-λ, TNF-α, and granzyme B, against various types of HER2-positive tumor cells in vitro, including A549, NCI-H460, SKOV-3, A1847, SKBR3, and MDA-MB-231. The bsAb-mediated antitumor effect is highly specific and strictly dependent on its binding to HER2, as evidenced by the gained resistance of A549 and A1847 her2 knockout cells and the acquired sensitivity of mouse 4T1 cells overexpressing the human HER2 extracellular domain (ECD) or epitope-containing subdomain IV to the bsAb-induced T cell cytotoxicity. The bsAb also relies on its binding to CD3 for T-cell recruitment, as ablation of CD3 binding abolished the bsAb’s ability to elicit antitumor activity. Importantly, intratumoral injection of the HER2-CD3-Fc mRNA-LNPs triggers a strong antitumor response and completely blocks HER2-positive tumor growth in a mouse xenograft model of human ovarian cancer. These results indicate that the novel HER2-CD3-Fc mRNA-LNP-based therapy has the potential to effectively treat HER2-positive cancer. Full article
(This article belongs to the Special Issue Immunotherapy for Cancers)
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