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Advances in Cancer Immunotherapy and Vaccines Research

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 24834

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Dr. Takumi Kumai

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Department of Otolaryngology Head and Neck Surgery, Asahikawa Medical University, Midorigaoka East 2-1-1-1, Asahikawa, Hokkaido 0788510, Japan
Interests: tumor vaccine; T-cells; peptides; adjuvants; head and neck cancer
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Special Issue Information

Dear Colleagues,

Immunotherapy has emerged as a standard therapy in addition to surgical resection, chemotherapy, and radiotherapy. The oncological outcome of immune checkpoint blockades is acceptable in a variety of tumor types, indicating immune cells’ ability to kill tumors. The drawback of immune checkpoint blockades is their low responder rate of around 20%. As the effect of immune checkpoint blockades depends on already-existing immune cells in the tumor microenvironment, the lack, or exhaustion, of these cells hinders the antitumor effect of this treatment. A tumor vaccine specifically increases antitumor immune cells. In addition to CD8 T-cells, which play an essential role in tumor vaccination by directly killing tumor cells, innumerable reports have indicated that CD4 T-cells also have direct cytotoxic activity against tumors. The identification of peptide epitopes from tumor-associated antigens (TAA) could aid the development of a tumor vaccine. However, vaccination using tumor-derived peptides and inadequate adjuvants, such as incomplete Freund’s adjuvant (IFA), which consists of non-metabolizable oil and a surfactant, failed to achieve clinical antitumor effects in the late 20^th century. With advances in the understanding of the immune system, we now have a solid theory for the expansion of T-cells by combining peptides (T-cell receptor stimulation as signal 1, costimulatory molecules as signal 2, and cytokines as signal 3) using adequate adjuvants and impeding the immune-suppressive environment. This Special Issue will gather the latest advances in the field of tumor immunology to optimize a tumor vaccine.

Potential topics for this Special Issue include, but are not limited to, the following:

- Immune adjuvants for a tumor vaccine;

- Immunological assessment of the tumor microenvironment;

- Combination of immunotherapy and chemoradiotherapy;

- Optimization of administration route and/or formula in a tumor vaccine;

- Immune cell polarization and immunotherapy;

- Impeding immune suppression in the tumor microenvironment;

- Re-education of immune cells in the tumor microenvironment;

Dr. Takumi Kumai
Guest Editor

Manuscript Submission Information

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Keywords

tumor vaccine
immune adjuvants
tumor immune environment
peptide vaccine
chemoradiotherapy
cytokines
suppressive immune cells
checkpoint inhibitors

Published Papers (10 papers)

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Research

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15 pages, 1689 KiB

Open AccessArticle

Usefulness of Docking and Molecular Dynamics in Selecting Tumor Neoantigens to Design Personalized Cancer Vaccines: A Proof of Concept

by Diego Amaya-Ramirez, Laura Camila Martinez-Enriquez and Carlos Parra-López

Vaccines 2023, 11(7), 1174; https://doi.org/10.3390/vaccines11071174 - 29 Jun 2023

Cited by 2 | Viewed by 1238

Abstract

Personalized cancer vaccines based on neoantigens are a new and promising treatment for cancer; however, there are still multiple unresolved challenges to using this type of immunotherapy. Among these, the effective identification of immunogenic neoantigens stands out, since the in silico tools used generate a significant portion of false positives. Inclusion of molecular simulation techniques can refine the results these tools produce. In this work, we explored docking and molecular dynamics to study the association between the stability of peptide–HLA complexes and their immunogenicity, using as a proof of concept two HLA-A2-restricted neoantigens that were already evaluated in vitro. The results obtained were in accordance with the in vitro immunogenicity, since the immunogenic neoantigen ASTN1 remained bound at both ends to the HLA-A2 molecule. Additionally, molecular dynamic simulation suggests that position 1 of the peptide has a more relevant role in stabilizing the N-terminus than previously proposed. Likewise, the mutations may have a “delocalized” effect on the peptide–HLA interaction, which means that the mutated amino acid influences the intensity of the interactions of distant amino acids of the peptide with the HLA. These findings allow us to propose the inclusion of molecular simulation techniques to improve the identification of neoantigens for cancer vaccines. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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13 pages, 1257 KiB

Open AccessArticle

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study

by Scott R. Burkholz, Charles V. Herst, Richard T. Carback, Paul E. Harris and Reid M. Rubsamen

Vaccines 2023, 11(3), 644; https://doi.org/10.3390/vaccines11030644 - 13 Mar 2023

Cited by 5 | Viewed by 2911

Abstract

A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3–4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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21 pages, 8084 KiB

Open AccessArticle

Design and In Silico Validation of a Novel MZF-1-Based Multi-Epitope Vaccine to Combat Metastatic Triple Negative Breast Cancer

by HemaNandini Rajendran Krishnamoorthy and Ramanathan Karuppasamy

Vaccines 2023, 11(3), 577; https://doi.org/10.3390/vaccines11030577 - 2 Mar 2023

Cited by 3 | Viewed by 2402

Abstract

Immunotherapy is emerging as a potential therapeutic strategy for triple negative breast cancer (TNBC) owing to the immunogenic landscape of its tumor microenvironment. Interestingly, peptide-based cancer vaccines have garnered a lot of attention as one of the most promising cancer immunotherapy regimens. Thus, the present study intended to design a novel, efficacious peptide-based vaccine against TNBC targeting myeloid zinc finger 1 (MZF1), a transcription factor that has been described as an oncogenic inducer of TNBC metastasis. Initially, the antigenic peptides from MZF1 were identified and evaluated based on their likelihood to induce immunological responses. The promiscuous epitopes were then combined using a suitable adjuvant (50S ribosomal L7/L12 protein) and linkers (AAY, GPGPG, KK, and EAAAK) to reduce junctional immunogenicity. Furthermore, docking and dynamics analyses against TLR-4 and TLR-9 were carried out to understand more about their structural stability and integrity. Finally, the constructed vaccine was subjected to in silico cloning and immune simulation studies. Overall, the findings imply that the designed chimeric vaccine could induce strong humoral and cellular immune responses in the desired organism. In light of these findings, the final multi-epitope vaccine could be used as an effective prophylactic treatment for TNBC and may pave the way for future research. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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23 pages, 5244 KiB

Open AccessArticle

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches

by Mukhtar Ahmad Dar, Pawan Kumar, Prakash Kumar, Ashish Shrivastava, Muneer Ahmad Dar, Richa Chauhan, Vinita Trivedi, Ashutosh Singh, Eshan Khan, Ravichandiran Velayutham and Sameer Dhingra

Vaccines 2022, 10(11), 1850; https://doi.org/10.3390/vaccines10111850 - 31 Oct 2022

Cited by 3 | Viewed by 2508

Abstract

Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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Review

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24 pages, 4672 KiB

Open AccessReview

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

by Liusheng Wu, Xiaoqiang Li, Xinye Qian, Shuang Wang, Jixian Liu and Jun Yan

Vaccines 2024, 12(2), 186; https://doi.org/10.3390/vaccines12020186 - 12 Feb 2024

Cited by 1 | Viewed by 2479

Abstract

In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells in cancer therapy has become a strategy of great research interest. mRNA vaccines are a potential choice for tumor immunotherapy, due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery carrier, and their structural stability and biocompatibility make them an effective means for delivering mRNA to specific targets. This study summarizes the research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity, and targeting is discussed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy, as well as to provide more effective treatment plans for patients. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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18 pages, 832 KiB

Open AccessReview

Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines

by Francisca Palomares, Alejandra Pina, Hala Dakhaoui, Camila Leiva-Castro, Ana M. Munera-Rodriguez, Marta Cejudo-Guillen, Beatriz Granados, Gonzalo Alba, Consuelo Santa-Maria, Francisco Sobrino and Soledad Lopez-Enriquez

Vaccines 2024, 12(2), 165; https://doi.org/10.3390/vaccines12020165 - 6 Feb 2024

Viewed by 1508

Abstract

Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis. In this review, we examine the current state of development and progress of vaccines in AML. The findings evidence the possible administration of DC-based vaccines as an adjuvant treatment in AML following initial therapy. Furthermore, the therapy demonstrates promising outcomes in preventing or delaying tumor relapse and exhibits synergistic effects when combined with other treatments during relapses or disease progression. On the other hand, the remarkable success observed with RNA vaccines for COVID-19, delivered in lipid nanoparticles, has revealed the efficacy and effectiveness of these types of vectors, prompting further exploration and their potential application in AML, as well as other neoplasms, loading them with tumor RNA. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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17 pages, 1428 KiB

Open AccessReview

Harnessing Immunity to Treat Advanced Thyroid Cancer

by Hiroki Komatsuda, Michihisa Kono, Risa Wakisaka, Ryosuke Sato, Takahiro Inoue, Takumi Kumai and Miki Takahara

Vaccines 2024, 12(1), 45; https://doi.org/10.3390/vaccines12010045 - 30 Dec 2023

Viewed by 1603

Abstract

The incidence of thyroid cancer (TC) has increased over the past 30 years. Although differentiated thyroid cancer (DTC) has a good prognosis in most patients undergoing total thyroidectomy followed by radioiodine therapy (RAI), 5–10% of patients develop metastasis. Anaplastic thyroid cancer (ATC) has a low survival rate and few effective treatments have been available to date. Recently, tyrosine kinase inhibitors (TKIs) have been successfully applied to RAI-resistant or non-responsive TC to suppress the disease. However, TC eventually develops resistance to TKIs. Immunotherapy is a promising treatment for TC, the majority of which is considered an immune-hot malignancy. Immune suppression by TC cells and immune-suppressing cells, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, is complex and dynamic. Negative immune checkpoints, cytokines, vascular endothelial growth factors (VEGF), and indoleamine 2,3-dioxygenase 1 (IDO1) suppress antitumor T cells. Basic and translational advances in immune checkpoint inhibitors (ICIs), molecule-targeted therapy, tumor-specific immunotherapy, and their combinations have enabled us to overcome immune suppression and activate antitumor immune cells. This review summarizes current findings regarding the immune microenvironment, immunosuppression, immunological targets, and immunotherapy for TC and highlights the potential efficacy of immunotherapy. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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19 pages, 704 KiB

Open AccessReview

The Role of TRL7/8 Agonists in Cancer Therapy, with Special Emphasis on Hematologic Malignancies

by Maria Leśniak, Justyna Lipniarska, Patrycja Majka, Weronika Kopyt, Monika Lejman and Joanna Zawitkowska

Vaccines 2023, 11(2), 277; https://doi.org/10.3390/vaccines11020277 - 28 Jan 2023

Cited by 1 | Viewed by 3658

Abstract

Toll-like receptors (TLR) belong to the pattern recognition receptors (PRR). TLR7 and the closely correlated TLR8 affiliate with toll-like receptors family, are located in endosomes. They recognize single-stranded ribonucleic acid (RNA) molecules and synthetic deoxyribonucleic acid (DNA)/RNA analogs—oligoribonucleotides. TLRs are primarily expressed in hematopoietic cells. There is compiling evidence implying that TLRs also direct the formation of blood cellular components and make a contribution to the pathogenesis of certain hematopoietic malignancies. The latest research shows a positive effect of therapy with TRL agonists on the course of hemato-oncological diseases. Ligands impact activation of antigen-presenting cells which results in production of cytokines, transfer of mentioned cells to the lymphoid tissue and co-stimulatory surface molecules expression required for T-cell activation. Toll-like receptor agonists have already been used in oncology especially in the treatment of dermatological neoplastic lesions. The usage of these substances in the treatment of solid tumors is being investigated. The present review discusses the direct and indirect influence that TLR7/8 agonists, such as imiquimod, imidazoquinolines and resiquimod have on neoplastic cells and their promising role as adjuvants in anticancer vaccines. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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11 pages, 1158 KiB

Open AccessPerspective

The Limitations of Current T Cell-Driven Anticancer Immunotherapies Can Be Overcome with an Original Extracellular-Vesicle-Based Vaccine Strategy

by Maurizio Federico

Vaccines 2023, 11(12), 1847; https://doi.org/10.3390/vaccines11121847 - 13 Dec 2023

Viewed by 991

Abstract

The emergence of tumors associated with defects in immune surveillance often involve the impairment of key functions of T lymphocytes. Therefore, several anticancer immunotherapies have focused on the induction/strengthening of the tumor-specific activity of T cells. In particular, strategies based on immune checkpoint inhibitors, CAR-T cells, and mRNA vaccines share a common goal of inducing/recovering an effective antitumor cytotoxic activity, often resulting in either exhausted or absent in patients’ lymphocytes. In many instances, these approaches have been met with success, becoming part of current clinic protocols. However, the most practiced strategies sometimes also pay significant tolls in terms of adverse events, a lack of target specificity, tumor escape, and unsustainable costs. Hence, new antitumor immunotherapies facing at least some of these issues need to be explored. In this perspective article, the characteristics of a novel CD8⁺ T cell-specific anticancer vaccine strategy based on in vivo-engineered extracellular vesicles are described. How this approach can be exploited to overcome at least some of the limitations of current antitumor immunotherapies is also discussed. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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40 pages, 1117 KiB

Open AccessSystematic Review

Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review

by Mina Hosseini, Simin Seyedpour, Behzad Khodaei, Amir-Hossein Loghman, Nasrin Seyedpour, Mohammad-Hossein Yazdi and Nima Rezaei

Vaccines 2023, 11(1), 146; https://doi.org/10.3390/vaccines11010146 - 9 Jan 2023

Cited by 17 | Viewed by 4623

Abstract

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the poorest outcomes, and is associated with a high risk of relapse and metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due to a lack of expression of the canonical molecular targets. Immunotherapy has been recently changing the treatment paradigm for many types of tumors, and the approach of evoking active immune responses in the milieu of breast tumors through cancer vaccines has been introduced as one of the most novel immunotherapeutic approaches. Accordingly, a number of vaccines for the treatment or prevention of recurrence have been developed and are currently being studied in TNBC patients, while none have yet received any approvals. To elucidate the efficacy and safety of these vaccines, we performed a systematic review of the available literature on the topic. After searching the PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL, and Google Scholar databases, a total of 5701 results were obtained, from which 42 clinical studies were eventually included based on the predefined criteria. The overall quality of the included studies was acceptable. However, due to a lack of reporting outcomes of survival or progression in some studies (which were presented as conference abstracts) as well as the heterogeneity of the reported outcomes and study designs, we were not able to carry out a meta-analysis. A total of 32 different vaccines have so far been evaluated in TNBC patients, with the majority belonging to the peptide-based vaccine type. The other vaccines were in the cell or nucleic acid (RNA/DNA)-based categories. Most vaccines proved to be safe with low-grade, local adverse events and could efficiently evoke cellular immune responses; however, most trials were not able to demonstrate significant improvements in clinical indices of efficacy. This is in part due to the limited number of randomized studies, as well as the limited TNBC population of each trial. However, due to the encouraging results of the currently published trials, we anticipate that this strategy could show its potential through larger, phase III randomized studies in the near future. Full article

(This article belongs to the Special Issue Advances in Cancer Immunotherapy and Vaccines Research)

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