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Clinical Applications of Tumor Immunotherapy
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Clinical Applications of Tumor Immunotherapy

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (16 September 2024) | Viewed by 9362

Special Issue Editors

Dr. Giuseppe Lamberti

E-Mail Website
Guest Editor
Department of Specialized, Experimental and Diagnostic Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
Interests: neuroendocrine tumors; small-cell lung cancer; immunotherapy; clinical research; precision oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Elisa Andrini

E-Mail Website
Guest Editor
Department of Specialized, Experimental and Diagnostic Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
Interests: neuroendocrine tumors; small-cell lung cancer; immunotherapy; clinical research; precision oncology

Special Issue Information

Dear Colleagues,

The advent of tumor immunotherapy had a significant impact on the treatment landscape of several hematological and solid tumors. The use of immune checkpoint inhibitors (ICIs) is by far the strategy with the most dramatic impact and widest adoption in tumor immunotherapy. These agents block inhibitory interactions between cancer and immune cells, thus prompting antitumor immunity and averting tumor evasion of the immune response. Adoptive cell therapies, such as chimeric antigen receptor T (CAR-T) cells, have been proven to be effective in some hematologic malignancies, with uncertain results in solid tumors. Several other tumor immunotherapy approaches, e.g., therapeutic vaccines and bispecific T cell engagers (BiTE), among others, are actively investigated, with promising results.

Irrespective of the type considered, tumor immunotherapies yielded unprecedented benefits in hard-to-treat tumors in terms of long-lasting responses and the prolongation of survival outcomes, with a peculiar toxicity profile that can be insidious. Research on tumor immunotherapy is brisk and active, currently focusing on how to increase the proportion of patients that benefit from different immunotherapy approaches and on identifying predictive biomarkers of response; thus, it is critical to understand how available evidence and findings, as well as future perspectives, translate into resources for clinical practice.

Dr. Giuseppe Lamberti
Dr. Elisa Andrini
Guest Editors

Manuscript Submission Information

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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

  • immunotherapy
  • PD-1/PD-L1
  • CTLA-4
  • novel biomarkers
  • personalized oncology
  • tumor vaccine
  • cell therapy
  • adoptive immunotherapy
  • T cell engagers

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Published Papers (6 papers)

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Research

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8 pages, 191 KiB  
Article
Impact of Allogeneic Stem Cell Transplant on Safety and Outcomes of Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Patients with Multiple Myeloma (MM)
by Ayrton Bangolo, Behzad Amoozgar, Lili Zhang, Vignesh K. Nagesh, Imranjot Sekhon, Simcha Weissman, David Vesole, Pooja Phull, Michele Donato, Noa Biran, David Siegel and Harsh Parmar
J. Clin. Med. 2024, 13(20), 6207; https://doi.org/10.3390/jcm13206207 - 18 Oct 2024
Viewed by 1059
Abstract
Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and [...] Read more.
Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and graft-versus-host disease (GVHD). The possibility of GVHD exacerbation when CAR-T cells are administered to patients previously treated with allo-SCT remains a topic of concern. Ciltacabtagene autoleucel (Cilta-cel) and idecabtagene vicleucel (Ide-cel) are CAR-T therapies that have been FDA-approved for relapsed/refractory (R/R) MM. A recent study using data from the CARTITUDE-1 trial has shown promising safety and efficacy of Cilta-Cel in patients with a prior history of allo-SCT. This report outlines our real-world experience with CAR-T treatment in such patients. The objective of this study is to assess the safety and effectiveness of CAR-T therapy in R/R MM patients who have previously undergone allo-SCT. Methods: We conducted a retrospective analysis of adult patients (18–70 years old) with R/R MM treated with CAR-T therapy as part of an institutional IRB-approved protocol. Data were collected on safety and efficacy outcomes from the institution’s records. Adverse events (AEs) were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Efficacy metrics included overall response rate (ORR) and progression-free survival (PFS), analyzed through the Kaplan–Meier method, with PFS defined as the time from CAR-T initiation to disease progression or death. Results: Of the 56 patients treated with CAR-T therapy, 8 (14.3%) had previously undergone allo-SCT. These patients had a median of seven prior therapy lines (LOTs), compared to five LOTs in the non-allo-SCT group (p = 0.04). CAR-T infusion occurred a median of 98.8 months after allo-SCT, with a range from 57.9 months to 178.5 months. CRS occurred in 87.5% of the allo-SCT group versus 77.1% in the non-allo-SCT group (p = 0.48). One patient in the allo-SCT group developed hemophagocytic lymphohistiocytosis (HLH), requiring anakinra. At a median follow-up of 4.8 months, the ORR was 87.5% in the allo-SCT group versus 75% in the non-allo-SCT group (p = 0.4). Median PFS had not been reached for the allo-SCT group at the time of analysis compared to 11.9 months in the non-allo-SCT group (p = 0.5). No treatment-related mortality or acute GVHD was noted in the allo-SCT cohort. Conclusions: The study suggests that prior allo-SCT does not adversely affect the safety or efficacy of CAR-T therapy in patients with R/R MM. These findings highlight the need for further investigations with larger patient samples and longer follow-up to better understand the interaction between allo-SCT and CAR-T therapy. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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12 pages, 1130 KiB  
Article
Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity
by Marina Pérez, Berta Buey, Pilar Corral, David Giraldos and Eva Latorre
J. Clin. Med. 2024, 13(13), 3885; https://doi.org/10.3390/jcm13133885 - 2 Jul 2024
Cited by 1 | Viewed by 1700
Abstract
Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have [...] Read more.
Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs’ production could play a fundamental role in cancer immunotherapy. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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14 pages, 816 KiB  
Article
A Systemic Immune Inflammation Index and PD-L1 (SP142) Expression as a Potential Combined Biomarker of the Clinical Benefit of Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer
by Jong-Min Baek, Hyungkeun Cha, Yeonsook Moon, Lucia Kim, Seung Min Kwak, Eun Sun Park and Hae-Seong Nam
J. Clin. Med. 2024, 13(5), 1521; https://doi.org/10.3390/jcm13051521 - 6 Mar 2024
Cited by 2 | Viewed by 1436
Abstract
Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive [...] Read more.
Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive value in ES-SCLC. We determined the best independent prognostic biomarker among the four complete blood-count-derived inflammatory biomarkers (CBC-IBs). Subsequently, we analyzed the prognostic or predictive value of combining this independent CBC-IB with PD-L1 (SP142) expression. We prospectively assessed the SP142 analyses in tumor samples at diagnosis. Results: All in all, 55 patients with ES-SCLC were classified into four groups according to the systemic immune inflammation index (SII) (low/high) and SP142 (positive/negative). The best survival was observed in the low-SII/ SP142-positive group, whereas the worst survival was observed in the high-SII/SP142-negative group (p = 0.002). The combined SII-SP142 biomarker was better for predicting both survival and disease progression in patients with ES-SCLC. Conclusions: The combined SII-SP142 biomarker can be readily and universally obtained at a low cost in clinical practice, without requiring advanced genomics technology or specialized expertise. Although further studies are needed to confirm that the combined SII-SP142 biomarker is widely applicable, it should help clinicians to identify the best patients for combined chemotherapy with atezolizumab in ES-SCLC. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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15 pages, 3271 KiB  
Article
DR5 Up-Regulation Induced by Dichloroacetate Sensitizes Tumor Cells to Lipid Nanoparticles Decorated with TRAIL
by Joaquín Marco-Brualla, Diego de Miguel, Luis Martínez-Lostao and Alberto Anel
J. Clin. Med. 2023, 12(2), 608; https://doi.org/10.3390/jcm12020608 - 12 Jan 2023
Cited by 3 | Viewed by 2179
Abstract
Cancer resistance to treatments is a challenge that researchers constantly seek to overcome. For instance, TNF-related apoptosis-inducing ligand (TRAIL) is a potential good prospect as an anti-cancer therapy, as it attacks tumor cells but not normal cells. However, treatments based in soluble TRAIL [...] Read more.
Cancer resistance to treatments is a challenge that researchers constantly seek to overcome. For instance, TNF-related apoptosis-inducing ligand (TRAIL) is a potential good prospect as an anti-cancer therapy, as it attacks tumor cells but not normal cells. However, treatments based in soluble TRAIL provided incomplete clinical results and diverse formulations have been developed to improve its bioactivity. In previous works, we generated a new TRAIL formulation based in its attachment to the surface of unilamellar nanoliposomes (LUV-TRAIL). This formulation greatly increased apoptosis in a wide selection of tumor cell types, albeit a few of them remained resistant. On the other hand, it has been described that a metabolic shift in cancer cells can also alter its sensitivity to other treatments. In this work, we sought to increase the sensitivity of several tumor cell types resistant to LUV-TRAIL by previous exposure to the metabolic drug dichloroacetate (DCA), which forces oxidative phosphorylation. Results showed that DCA + LUV-TRAIL had a synergistic effect on both lung adenocarcinoma A549, colorectal HT29, and breast cancer MCF7 cells. Despite DCA inducing intracellular changes in a cell-type specific way, the increase in cell death by apoptosis was clearly correlated with an increase in death receptor 5 (DR5) surface expression in all cell lines. Therefore, DCA-induced metabolic shift emerges as a suitable option to overcome TRAIL resistance in cancer cells. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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Review

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13 pages, 618 KiB  
Review
Novel Immune Checkpoint Inhibitor Targets in Advanced or Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives
by Samuele Compagno, Chiara Casadio, Linda Galvani, Matteo Rosellini, Andrea Marchetti, Elisa Tassinari, Pietro Piazza, Angelo Mottaran, Matteo Santoni, Riccardo Schiavina, Francesco Massari and Veronica Mollica
J. Clin. Med. 2024, 13(19), 5738; https://doi.org/10.3390/jcm13195738 - 26 Sep 2024
Viewed by 1441
Abstract
Immune checkpoint inhibitors (ICI) have become the cornerstone of treatment in renal cell carcinoma (RCC), for both metastatic disease and in an adjuvant setting. However, an adaptive resistance from cancer cells may arise during ICI treatment, therefore many studies are focusing on additional [...] Read more.
Immune checkpoint inhibitors (ICI) have become the cornerstone of treatment in renal cell carcinoma (RCC), for both metastatic disease and in an adjuvant setting. However, an adaptive resistance from cancer cells may arise during ICI treatment, therefore many studies are focusing on additional immune checkpoint inhibitor pathways. Promising targets of immunotherapeutic agents under investigation include T cell immunoglobulin and ITIM domain (TIGIT), immunoglobulin-like transcript 4 (ILT4), lymphocyte activation gene-3 (LAG-3), vaccines, T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and chimeric antigen receptor (CAR) T cells. In this review of the literature, we recollect the current knowledge of the novel treatment strategies in the field of immunotherapy that are being investigated in RCC and analyze their mechanism of action, their activity and the clinical studies that are currently underway. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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Other

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22 pages, 1400 KiB  
Perspective
Next-Generation Immunotherapy: Advancing Clinical Applications in Cancer Treatment
by Pankaj Garg, Siddhika Pareek, Prakash Kulkarni, David Horne, Ravi Salgia and Sharad S. Singhal
J. Clin. Med. 2024, 13(21), 6537; https://doi.org/10.3390/jcm13216537 - 30 Oct 2024
Viewed by 1144
Abstract
Next-generation immunotherapies have revolutionized cancer treatment, offering hope for patients with hard-to-treat tumors. This review focuses on the clinical applications and advancements of key immune-based therapies, including immune checkpoint inhibitors, CAR-T cell therapy, and new cancer vaccines designed to harness the immune system [...] Read more.
Next-generation immunotherapies have revolutionized cancer treatment, offering hope for patients with hard-to-treat tumors. This review focuses on the clinical applications and advancements of key immune-based therapies, including immune checkpoint inhibitors, CAR-T cell therapy, and new cancer vaccines designed to harness the immune system to combat malignancies. A prime example is the success of pembrolizumab in the treatment of advanced melanoma, underscoring the transformative impact of these therapies. Combination treatments, integrating immunotherapy with chemotherapy, radiation, and targeted therapies, are demonstrating synergistic benefits and improving patient outcomes. This review also explores the evolving role of personalized immunotherapy, guided by biomarkers, genomic data, and the tumor environment, to better target individual tumors. Although significant progress has been made, challenges such as resistance, side effects, and high treatment costs persist. Technological innovations, including nanotechnology and artificial intelligence, are explored as future enablers of these therapies. The review evaluates key clinical trials, breakthroughs, and the emerging immune-modulating agents and advanced delivery systems that hold great promise for enhancing treatment efficacy, reducing toxicity, and expanding access to immunotherapy. In conclusion, this review highlights the ongoing advancements in immunotherapy that are reshaping cancer care, with future strategies poised to overcome current challenges and further extend therapeutic reach. Full article
(This article belongs to the Special Issue Clinical Applications of Tumor Immunotherapy)
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