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Immunotherapy in Cancer

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 (28 February 2025) | Viewed by 629

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Guest Editor
Center for Cancer Immunology Research, Children’s National Hospital, Children’s National Research Institute, 111 Michigan Avenue NW, Washington, DC 20010, USA
Interests: cell biology; animal model; cancer
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Special Issue Information

Dear Colleagues,

Immunotherapy has emerged as a revolutionary approach in cancer treatment, offering new hope for patients with various malignancies (for example, solid tumors and hematological malignancies). By harnessing the body's immune system to target and eliminate cancer cells, immunotherapy has the potential to achieve long-lasting remission and even cures in certain cases. This innovative approach represents a significant shift from traditional cancer treatments, which primarily focus on directly targeting tumors through surgery, radiation, or chemotherapy. Despite its promise, immunotherapy faces several challenges, including the variability in patient responses, the development of resistance, and the occurrence of immune-related adverse events. These challenges underscore the complexity of the immune system's interaction with cancer and highlight the need for continued research to optimize treatment strategies.

This Special Issue will explore the current landscape of immunotherapy in cancer, focusing on the mechanisms by which the immune system can be activated or suppressed in the context of cancer. It will also examine the latest advances in immunotherapeutic agents, including immune checkpoint inhibitors; CAR-T, CAR-NK, and CAR-M cell therapy; cancer vaccines; cytokine therapies; and adoptive cell therapies. Furthermore, this Special Issue will address the challenges of immunotherapy, such as identifying biomarkers for response prediction, managing resistance, and minimizing toxicity. Finally, the implications of immunotherapy for the future of cancer treatment and the potential for combination therapies will be discussed, emphasizing the need for ongoing research and innovation in this rapidly evolving field. IJMS focuses on molecular studies in biology and chemistry, with a strong emphasis on molecular biology and molecular medicine, and we particularly welcome publications on molecular-level basic research.

Dr. Nethaji Muniraj
Guest Editor

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Keywords

  • immunotherapy
  • biomarkers
  • immune modulation
  • combination therapies
  • solid tumors
  • hematological malignancies

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Published Papers (1 paper)

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Research

19 pages, 4140 KiB  
Article
Enhancing the Anticancer Activity of a Carcinoma-Directed Peptide–HLA-I Fusion Protein by Armoring with Mutein IFNα
by Douwe Freerk Samplonius, Anne Paulien van Wijngaarden, Lisanne Koll, Xiurong Ke and Wijnand Helfrich
Int. J. Mol. Sci. 2025, 26(7), 3178; https://doi.org/10.3390/ijms26073178 - 29 Mar 2025
Viewed by 371
Abstract
Previously, we reported on the peptide–HLA-I fusion protein EpCAM-ReTARGTPR, which allows us to redirect the cytotoxic activity of pre-existing anti-CMV CD8pos T cell immunity to selectively eliminate EpCAMpos cancer cells. EpCAM-ReTARGTPR consists of the CMV pp65-derived peptide TPRVTGGGAM [...] Read more.
Previously, we reported on the peptide–HLA-I fusion protein EpCAM-ReTARGTPR, which allows us to redirect the cytotoxic activity of pre-existing anti-CMV CD8pos T cell immunity to selectively eliminate EpCAMpos cancer cells. EpCAM-ReTARGTPR consists of the CMV pp65-derived peptide TPRVTGGGAM (TPR) fused in tandem with a soluble HLA-B*07:02/β2-microglobulin (β2M) molecule and an EpCAM-directed Fab antibody fragment. To further enhance its anticancer activity, we equipped EpCAM-ReTARGTPR with the immune-potentiating cytokine muteins IL2(H16A,F42A) and IFNαR149A, respectively. Both cytokines are engineered to have attenuated affinity for their respective cytokine receptors. Compared to EpCAM-ReTARGTPR, in vitro treatment of EpCAMpos carcinoma cell lines with EpCAM-ReTARGTPRvIL2 for 24 h increased the cytotoxic activity of PBMCs containing low levels of TPR-specific CD8pos T cells by ~15%, whereas EpCAM-ReTARGTPRIFNαR149A induced an increase of ~50%. Moreover, treatment for 120 h with EpCAM-ReTARGTPRIFNαR149A inhibited the proliferative capacity of the cancer cell lines OvCAR3 and PC3M by ~91% without compromising the viability of the TPR-specific CD8pos T cells and increased their capacity for IFNγ secretion. Importantly, EpCAM-ReTARGTPRIFNαR149A potently induced the elimination of primary EpCAMpos refractory carcinoma cells from a Merkel cell carcinoma (MCC) patient. Taken together, the armoring of the carcinoma-directed peptide–HLA-I fusion protein EpCAM-ReTARGTPR with IFNαR149A potently enhanced the efficacy of pre-existing anti-CMV CD8pos T cell immunity to selectively eliminate EpCAMpos cancer cells. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer)
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