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Update on Immunotherapies for Cancer
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Update on Immunotherapies for Cancer

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

Deadline for manuscript submissions: 20 September 2025 | Viewed by 12749

Special Issue Editor

Dr. Peter Johannes Holst

E-Mail Website
Guest Editor
Department of Immunology and Microbiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
Interests: antigen design; vectorology; therapeutic vaccines; immunotherapy; virology

Special Issue Information

Dear Colleagues,

The cancer immunotherapy field has made great progress, with new overarching concepts demonstrating clinical successes in recent years. The initial successes of blocking or antibody-dependent cellular cytotoxicity (ADCC), inducing HER2-specific antibodies, are now complemented in clinical trials by a range of antibody–drug conjugates and bispecific and trispecific antibodies. Their potential for eliciting increasing clinical efficacy via combinatorial approaches will grow significantly with the implementation of new combinations with reduced toxicities and preserved or improved efficacies, such as the recently approved anti-PD1 and anti-LAG3 combination therapy. Tumor-infiltrating T cell therapies have proven their worth in phase 3 trials and been developed into a range of cloned TCR and chimeric antigen receptor cellular therapies that are conquering hematological malignancies. The oldest immunotherapy principle of supplying danger signals within tumors is becoming increasingly refined and diverse with the use of molecular adjuvants, oncolytic virotherapies, and chemotherapy and radiotherapies. Perhaps most excitingly, the last couple of years have shown the entry of a new generation of cancer vaccines that are technologically ambitious using genetically modified vectors, and we are starting to see clinical trials with treatment in the adjuvant setting where patients have minimal residual tumor burden. These pivotal technological and clinical changes now provide meaningful clinical benefits in solid tumors, including those with minimal mutational burden where the outlook for long-term meaningful responses would have previously looked poor. In this Special Edition of the International Journal of Molecular Sciences, we will highlight recent breakthroughs and point towards the major challenges remaining.      

Dr. Peter Johannes Holst
Guest Editor

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Keywords

  • cell therapies
  • monoclonal antibodies
  • molecular adjuvants
  • oncolytic therapies
  • immunogenic
  • chemotherapy and radiotherapy
  • cancer vaccines
  • immunodominance
  • neoantigens
  • clinical trials
  • tumor immune microenvironment

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Published Papers (4 papers)

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16 pages, 1351 KiB  
Review
Personalized Cancer Vaccines Go Viral: Viral Vectors in the Era of Personalized Immunotherapy of Cancer
by Laura Seclì, Guido Leoni, Valentino Ruzza, Loredana Siani, Gabriella Cotugno, Elisa Scarselli and Anna Morena D’Alise
Int. J. Mol. Sci. 2023, 24(23), 16591; https://doi.org/10.3390/ijms242316591 - 22 Nov 2023
Cited by 16 | Viewed by 4325
Abstract
The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, [...] Read more.
The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, primarily due to the advancement of innovative technologies for the identification of neoantigens and novel vaccine delivery platforms. Here, we review the emerging field of personalized cancer vaccination, with a focus on the use of viral vectors as a vaccine platform. The recent advancements in viral vector technology have led to the development of efficient production processes, positioning personalized viral vaccines as one of the preferred technologies. Many clinical trials have shown the feasibility, safety, immunogenicity and, more recently, preliminary evidence of the anti-tumor activity of personalized vaccination, fostering active research in the field, including further clinical trials for different tumor types and in different clinical settings. Full article
(This article belongs to the Special Issue Update on Immunotherapies for Cancer)
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14 pages, 2422 KiB  
Communication
Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion
by Joshua Tobias, Sandra Högler, Martin Raigel, Diego Shih-Chieh Lin, Yee Chao, Lukas Kenner, Erika Garner-Spitzer, Sharon Yavrom, Nicholas J. Ede, Christoph C. Zielinski, Michael Kundi and Ursula Wiedermann
Int. J. Mol. Sci. 2024, 25(1), 287; https://doi.org/10.3390/ijms25010287 - 24 Dec 2023
Cited by 1 | Viewed by 2456
Abstract
Her-2/neu-targeting therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, which is attributed to the upregulation of tumoral PD-L1 expression and the downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently [...] Read more.
Her-2/neu-targeting therapy by passive application with trastuzumab is associated with acquired resistance and subsequent metastasis development, which is attributed to the upregulation of tumoral PD-L1 expression and the downregulation of Her-2/neu. We aimed to investigate this association, following active immunization with our recently constructed B-cell peptide-based Her-2/neu vaccines in both preclinical and clinical settings. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and combined positive score (CPS) were applied to evaluate Her-2/neu and PD-L1 expression using a murine syngeneic tumor model for Her-2/neu lung metastases and tumor biopsies from a gastric cancer patient with disease progression. A significant and concomitant reduction in Her-2/neu and the upregulation of PD-L1 expression was observed in vaccinated mice after 45 days, but not after 30 days, of metastases development. A significant increase in tumor-infiltrating B lymphocytes was observed at both time points. The downregulation of Her-2/neu and the upregulation of PD-L1 were observed in a patient’s primary tumor at the disease progression time point but not prior to vaccination (Her-2/neu IHC: 3 to 0, FISH: 4.98 to 1.63; PD-L1 CPS: 0% to 5%). Our results further underline the need for combination therapy by targeting PD-L1 to prevent metastasis formation and immune evasion of Her-2/neu-positive and PD-L1-negative tumor cells. Full article
(This article belongs to the Special Issue Update on Immunotherapies for Cancer)
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17 pages, 1409 KiB  
Review
MET Oncogene Targeting for Cancer Immunotherapy
by Andrea Maria Lombardi, Dario Sangiolo and Elisa Vigna
Int. J. Mol. Sci. 2024, 25(11), 6109; https://doi.org/10.3390/ijms25116109 - 1 Jun 2024
Cited by 4 | Viewed by 1928
Abstract
The MET receptor is one of the main drivers of ‘invasive growth’, a multifaceted biological response essential during embryonic development and tissue repair that is usurped by cancer cells to induce and sustain the malignant phenotype. MET stands out as one of the [...] Read more.
The MET receptor is one of the main drivers of ‘invasive growth’, a multifaceted biological response essential during embryonic development and tissue repair that is usurped by cancer cells to induce and sustain the malignant phenotype. MET stands out as one of the most important oncogenes activated in cancer and its inhibition has been explored since the initial era of cancer-targeted therapy. Different approaches have been developed to hamper MET signaling and/or reduce MET (over)expression as a hallmark of transformation. Considering the great interest gained by cancer immunotherapy, this review evaluates the opportunity of targeting MET within therapeutic approaches based on the exploitation of immune functions, either in those cases where MET impairment is crucial to induce an effective response (i.e., when MET is the driver of the malignancy), or when blocking MET represents a way for potentiating the treatment (i.e., when MET is an adjuvant of tumor fitness). Full article
(This article belongs to the Special Issue Update on Immunotherapies for Cancer)
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16 pages, 1075 KiB  
Review
Cancer Vaccines: Recent Insights and Future Directions
by Aretia-Teodora Malacopol and Peter Johannes Holst
Int. J. Mol. Sci. 2024, 25(20), 11256; https://doi.org/10.3390/ijms252011256 - 19 Oct 2024
Cited by 2 | Viewed by 3103
Abstract
The field of cancer immunotherapy has seen incredible advancements in the past decades. mRNA-based cancer vaccines generating de novo T cell responses, particularly against tumor-specific antigens (TSAs), have demonstrated promising clinical outcomes and overcome diverse challenges. Despite the high potential of neoantigens to [...] Read more.
The field of cancer immunotherapy has seen incredible advancements in the past decades. mRNA-based cancer vaccines generating de novo T cell responses, particularly against tumor-specific antigens (TSAs), have demonstrated promising clinical outcomes and overcome diverse challenges. Despite the high potential of neoantigens to provide personalized immunotherapies through their tumor specificity and immunogenicity, challenges related to the scarcity of immunogenic neoepitopes have prompted continuous research towards finding new tumor-associated antigens (TAAs) and broader therapeutic frameworks, which may now learn from the genuine successes obtained with neoantigens. As an example, human endogenous retroviruses (HERVs) have emerged as potential alternatives to tumor neoantigens due to their high tumoral expression and ability to elicit both T cell reactivity and B cell responses associated with the efficacy of existing immunotherapies. This review aims to assess the status and limitations of TSA-directed mRNA cancer vaccines and the lessons that can be derived from these and checkpoint inhibitor studies to guide TAA vaccine development. We expect that shared B cell, CD4 and CD8 T cell antigen presentation will be key to stimulate continuous T cell expansion and efficacy for tumors that do not contain pre-existing tertiary lymphoid structures. When these structures are present in highly mutated tumors, the current checkpoint-based immunotherapies show efficacy even in immune privileged sites, and vaccines may hold the key to broaden efficacy to more tumor types and stages. Full article
(This article belongs to the Special Issue Update on Immunotherapies for Cancer)
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