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Biomedicines
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The Development of Cancer Immunotherapy
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The Development of Cancer Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 3564

Special Issue Editor

Prof. Dr. Satoshi Wada

E-Mail Website
Guest Editor
Department of Clinical Diagnostic Oncology, Showa University Clinical Research Institute for Clinical Pharmacology and Therapeutics, 6-11-11 kita-karasuyama, setagaya-ku, Tokyo 157-8577, Japan
Interests: cancer immunotherapy; biomarker; CAR-T; Immune checkpoint inhibitor; pancreatic cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The clinical development of cancer immunotherapy has been progressing rapidly, and since the Nobel Prize in Physiology or Medicine in 2018 was awarded in this area, it has been attracting more attention than ever before and is expected to develop further in the future. Immune checkpoint inhibitors were developed as drugs with a completely different mechanism to conventional chemotherapy for cancer patients, and their therapeutic effects were characterized not only by tumor shrinkage, but also by the long-term survival of cancer patients, which had a strong impact on cancer treatment. On the other hand, as a result of numerous clinical trials, it was found that the efficacy of immune checkpoint inhibitors alone is only approximately 10–20%. Another cancer immunotherapy, genetically modified T-cell therapy, has shown high efficacy against hematological cancers, but its effectiveness against solid tumors is yet to be proven. The aim of this Special Issue is to further develop cancer immunotherapy.

Prof. Dr. Satoshi Wada
Guest Editor

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • cancer immunotherapy
  • immune checkpoint inhibitors
  • genetically modified T-cell therapy
  • hematological cancers
  • solid tumors

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Related Special Issue

Published Papers (4 papers)

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22 pages, 5751 KiB  
Article
Targeting Aggressive Prostate Carcinoma Cells with Mesothelin-CAR-T Cells
by Apolline de Testas de Folmont, Angèle Fauvel, Francis Vacherot, Pascale Soyeux, Abdérémane Abdou, Salem Chouaib and Stéphane Terry
Biomedicines 2025, 13(5), 1215; https://doi.org/10.3390/biomedicines13051215 - 16 May 2025
Viewed by 166
Abstract
Background: Advancing chimeric antigen receptor (CAR) T cell therapy for solid tumors remains a major challenge in cancer immunotherapy. Prostate cancer (PCa), particularly in its aggressive forms, may be a suitable target for CAR-T therapy given the range of associated tumor antigens. [...] Read more.
Background: Advancing chimeric antigen receptor (CAR) T cell therapy for solid tumors remains a major challenge in cancer immunotherapy. Prostate cancer (PCa), particularly in its aggressive forms, may be a suitable target for CAR-T therapy given the range of associated tumor antigens. However, due to the high plasticity and heterogeneity of aggressive PCa and the complexity of the tumor environment, there is a need to broaden the repertoire of targetable antigens and deepen our understanding of CAR-T behavior in stressed microenvironmental conditions. Growing evidence supports mesothelin as a promising cancer-associated marker and a compelling target for CAR-T cell approaches in solid tumors. Objectives and Methods: Here, we employed gene expression datasets to investigate mesothelin expression in both primary and metastatic PCa tumors. Additionally, we evaluated mesothelin expression across various preclinical PCa models and assessed the therapeutic efficacy of second-generation mesothelin-targeted CAR-T (meso-CAR-T) cells under both normoxic and hypoxic conditions, with hypoxia as a representative tumor-associated stress condition. Results: Our results revealed a significant enrichment of mesothelin in 3–10% of metastatic prostate tumors, contrasting with its minimal expression in primary tumors. In line with these findings, we observed increased mesothelin expression in an aggressive variant of the 22Rv1 cell line, which displayed an epithelial–mesenchymal plasticity (EMP) phenotype. Meso-CAR-T cells demonstrated potent cytotoxicity and remarkable selectivity toward these carcinoma cells under both severe hypoxia (1% O2) or normoxia (21% O2), highlighting their ability to withstand metabolic stress within the tumor microenvironment. Conclusions: Our study underscores the potential of meso-CAR-T cells as a promising strategy for targeting specific subtypes of metastatic prostate cancer. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy)
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15 pages, 2163 KiB  
Article
Using a Natural Triterpenoid to Unlock the Antitumor Effects of Autophagy in B-Cell Lymphoma
by Bently P. Doonan, Faisal F. Y. Radwan, Naren L. Banik and Azizul Haque
Biomedicines 2025, 13(2), 445; https://doi.org/10.3390/biomedicines13020445 - 12 Feb 2025
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Abstract
Background and Objective: Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin’s lymphoma, is the most common lymphoid malignancy in the Western world. Treatment of DLBCL has been greatly improved in recent years with the addition of the monoclonal antibody Rituximab to the [...] Read more.
Background and Objective: Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin’s lymphoma, is the most common lymphoid malignancy in the Western world. Treatment of DLBCL has been greatly improved in recent years with the addition of the monoclonal antibody Rituximab to the gold standard CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) chemotherapy regimen, but these treatments are often ineffective in patients with highly aggressive disease or patients of advanced age. While CAR-T cells have further advanced the treatment landscape of DLBCL, these often come at significant costs such as toxicity and financial costs for patients. Thus, research has recently focused on natural products that can selectively target malignant lymphomas while displaying a reduced host toxicity profile. Methods: In vitro cellular and biochemical approaches were used to analyze the effects of a natural extract from the Ganoderma lucidum mushroom (GA-DM) on autophagy and apoptosis in human and mouse B-cell lymphoma lines. In addition, in vivo approaches were applied to determine the effect of GA-DM on tumor growth and metastasis in a mouse model of B-cell lymphoma. Results: Here, we report, for the first time, that GA-DM induces apoptosis in the human B-cell lymphoma cell lines DB and Toledo, and orchestrates autophagy and apoptosis in the murine B-cell lymphoma cell line A20. While GA-DM differentially induced autophagy and apoptosis in mouse and human B-cell lymphomas, blocking apoptosis by the caspase inhibitor Z-VAD-FM reduced anti-proliferative activity in human B-cell lymphoma cells (DB: 71.6 ± 6.2% vs. 56.7 ± 2.4%; Toledo: 53.1 ± 10.6% vs. 14.6 ± 9.3%) in vitro. Antitumor efficacy of GA-DM was also investigated in vivo in a murine B-cell lymphoma model using the A20 cell line, where GA-DM treatment reduced both the number of tumor metastases (control: 5.5 ± 3.2 vs. GA-DM: 1.6 ± 0.87) and the overall tumor burden (control: 3.2 g ± 1.9 vs. GA-DM: 1.70 g ± 0.2) in diseased mice. Conclusions: These findings support the potential use of GA-DM as a novel chemotherapeutic in the treatment of DLBCL and could improve the treatment of higher-risk patients with advanced disease who cannot tolerate current chemotherapy treatments. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy)
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9 pages, 446 KiB  
Article
Combination of Brentuximab Vedotin and Pembrolizumab as Salvage Treatment Before Autologous Stem Cell Transplantation and Maintenance in Patients with Relapsed/Refractory Hodgkin Lymphoma
by Hanne Massa, Fulvio Massaro and Marie Maerevoet
Biomedicines 2025, 13(2), 252; https://doi.org/10.3390/biomedicines13020252 - 21 Jan 2025
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Abstract
Background: In relapsed or refractory classical Hodgkin lymphoma, achieving complete remission on 18FDG PET-CT before autologous stem cell transplantation improves progression-free survival. However, the optimal salvage therapy to achieve this remains undefined. Brentuximab vedotin combined with PD1 inhibitors has shown promise, though limited [...] Read more.
Background: In relapsed or refractory classical Hodgkin lymphoma, achieving complete remission on 18FDG PET-CT before autologous stem cell transplantation improves progression-free survival. However, the optimal salvage therapy to achieve this remains undefined. Brentuximab vedotin combined with PD1 inhibitors has shown promise, though limited data exist on the combination of brentuximab vedotin and pembrolizumab. Methods: We retrospectively collected data from 24 adult patients with confirmed relapsed or refractory classical Hodgkin lymphoma, who started salvage treatment with brentuximab vedotin and pembrolizumab with the intention of consolidation with high-dose chemotherapy, followed by autologous stem cell transplantation and brentuximab vedotin maintenance. Results: After two cycles of brentuximab vedotin and pembrolizumab, 95.2% achieved an overall response and 81.0% achieved complete metabolic response. 20 patients (83.3%) were in complete response at the end of maintenance, of whom one relapsed at 28 months after the end of treatment. Grade 3 and 4 toxicities during salvage treatment consisted mainly of hematological toxicity, one thyrotoxicosis, one hemophagocytic lymphohistiocytosis, and one arthralgia. Non-hematological grade 3–4 toxicities following transplantation were an inflammatory pneumonitis and one cryptococcal meningitis. One death occurred during prolonged post-transplant aplasia. During maintenance, dose reductions for toxicity were necessary in 16 patients, mainly due to peripheral neuropathy. Conclusions: For heavily pretreated relapsed or refractory classical Hodgkin lymphoma patients, our data suggest that salvage therapy with brentuximab vedotin and pembrolizumab before autologous stem cell transplantation followed by brentuximab vedotin maintenance is a highly active strategy, with acceptable toxicities. Further studies with larger cohorts are necessary to confirm these data. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy)
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25 pages, 1459 KiB  
Systematic Review
Nephrotoxicity of Immune Checkpoint Inhibitors in Single and Combination Therapy—A Systematic and Critical Review
by Javier Tascón, Alfredo G. Casanova, Laura Vicente-Vicente, Francisco J. López-Hernández and Ana I. Morales
Biomedicines 2025, 13(3), 711; https://doi.org/10.3390/biomedicines13030711 - 13 Mar 2025
Viewed by 684
Abstract
Background/Objectives: Immune checkpoint inhibitors (ICIs) have generated a revolutionary approach in the treatment of cancer, but their effectiveness has been compromised by immune-related adverse events, including renal damage. Although rare, these effects are relevant because they have been related to poor patient prognoses. [...] Read more.
Background/Objectives: Immune checkpoint inhibitors (ICIs) have generated a revolutionary approach in the treatment of cancer, but their effectiveness has been compromised by immune-related adverse events, including renal damage. Although rare, these effects are relevant because they have been related to poor patient prognoses. The objective of this review was to estimate the current incidence of nephrotoxicity in patients treated with single and double ICI therapies. Methods: A total of 1283 potential articles were identified, which were reduced to 50 after applying the exclusion and inclusion criteria. Results: This study reveals the increase in acute kidney injury associated with these drugs in the last decade and shows that, interestingly, combined therapies with ICIs does not lead to an increase in kidney damage compared with anti-CTLA-4. It also suggests that kidney damage could be underdiagnosed when it comes to interstitial nephritis, because definitive evidence requires a renal biopsy. Conclusions: In perspective, these conclusions could guide clinicians in making decisions for therapy personalization and highlight the need to search for new diagnostic systems that are more sensitive and specific to the type of damage and could replace the biopsy. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy)
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