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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 (30 April 2021) | Viewed by 63931

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Special Issue Editors

Prof. Wilbur B. Bowne

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Guest Editor

Department of Surgery, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: cell-cycle regulation; peptide therapeutics - pancreatic cancer; pancreatic and liver disease; serologic tumor marker detection; oncoproteins; early tumor detection; evaluation of abdominal masses

Dr. Adam E. Snook

E-Mail Website
Guest Editor

Department of Pharmacology & Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: guanylyl cyclases; intestinal epithelial cell biology; GI malignancies; colorectal cancer; targeted therapeutics; cancer mucosal antigens; cancer vaccines; immune tolerance; adoptive cell therapy
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Special Issue Information

Dear Colleagues,

Cancer immunotherapy has gained considerable popularity and momentum in recent years. Cancer vaccines, consisting of preventive and therapeutic vaccines, work by inducing or augmenting the immune response to enhance the immune system’s ability to fight cancer. Innovations for construction of cancer vaccines have emerged from advances in molecular immunology and cancer biology. Generally, vaccines combined with various adjuvants have been used to exploit the immune repertoire to induce antitumor immunity against specific tumor-associated antigens to overcome ignorance and tolerance to cancer cells. As a result, a multitude of cancer treatment vaccines has shown considerable promise in preclinical studies with subsequent development thus far of only a single FDA-approved vaccine.

Recent historic advances in immunotherapy underscore our continued quest for novel modern approaches to the treatment of cancer. It is becoming increasingly more apparent that a paradigm shift toward combination therapy might serve as a better treatment option compared to monotherapy to unleash a robust immune response against tumors. Combination regimens currently being explored with cancer vaccines include differing immunotherapeutic approaches involving immune checkpoint inhibitor therapy, monoclonal antibodies, adoptive cancer therapy, conventional chemotherapy and radiation therapy, which could be widely employed to target the tumor and associated microenvironment.

This Special Issue focuses on cancer vaccines and immunotherapy research. Submission of original articles, systematic reviews, short communications, and other types of article on related topics are welcome. Manuscripts will follow standard Journal peer-review practices, and those accepted for publication will appear in the special issue on Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment. We look forward to receiving and welcome your contributions.

Prof. Wilbur B. Bowne
Dr. Adam E. Snook
Guest Editors

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. Vaccines 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 2700 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 vaccines
cancer immunotherapy
preventive and therapeutic vaccines
adjuvant
combination therapy
immune checkpoint inhibitor therapy
monoclonal antibodies
adoptive cancer therapy
conventional chemotherapy/radiation therapy
tumor microenvironment

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

5 pages, 200 KiB

Open AccessEditorial

Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment

by Jagmohan Singh, Wilbur B. Bowne and Adam E. Snook

Vaccines 2021, 9(11), 1298; https://doi.org/10.3390/vaccines9111298 - 9 Nov 2021

Cited by 13 | Viewed by 2605

Abstract

In this editorial, we highlight articles published in this Special Issue of Vaccines on “Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment”, recent developments in the field of cancer vaccines, and the potential for immunotherapeutic combinations in cancer care. This issue covers important developments and progress being made in the cancer vaccine field and possible future directions for exploring new technologies to produce optimal immune responses against cancer and expand the arena of prophylactic and therapeutic cancer vaccines for the treatment of this deadly disease. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

Research

Jump to: Editorial, Review

13 pages, 1180 KiB

Open AccessArticle

Regional Delivery of Anti-PD-1 Agent for Colorectal Liver Metastases Improves Therapeutic Index and Anti-Tumor Activity

by Louis F. Chai, John C. Hardaway, Kara R. Heatherton, Kyle P. O’Connell, Mikayla C. Lopes, Benjamin A. Rabinowitz, Chandra C. Ghosh, Prajna Guha, David Jaroch, Bryan F. Cox and Steven C. Katz

Vaccines 2021, 9(8), 807; https://doi.org/10.3390/vaccines9080807 - 21 Jul 2021

Cited by 3 | Viewed by 3136

Abstract

Metastatic liver tumors have presented challenges with the use of checkpoint inhibitors (CPIs), with only limited success. We hypothesize that regional delivery (RD) of CPIs can improve activity in the liver and minimize systemic exposure, thereby reducing immune-related adverse events (irAE). Using a murine model of colorectal cancer liver metastases (LM), we confirmed high levels of PD-L1 expression on the tumor cells and liver myeloid-derived suppressor cells (L-MDSC). In vivo, we detected improved LM response at 3 mg/kg on PTD7 via portal vein (PV) regional delivery as compared to 3 mg/kg via tail vein (TV) systemic delivery (p = 0.04). The minimal effective dose at PTD7 was 5 mg/kg (p = 0.01) via TV and 0.3 mg/kg (p = 0.02) via PV. We detected 6.7-fold lower circulating CPI antibody levels in the serum using the 0.3 mg/kg PV treatment compared to the 5 mg/kg TV cohort (p < 0.001) without increased liver toxicity. Additionally, 3 mg/kg PV treatment resulted in increased tumor cell apoptotic signaling compared to 5 mg/kg TV (p < 0.05). Therefore, RD of an anti-PD-1 CPI therapy for CRCLM may improve the therapeutic index by reducing the total dose required and limiting the systemic exposure. These advantages could expand CPI indications for liver tumors. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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20 pages, 3032 KiB

Open AccessArticle

Targeted Delivery of BZLF1 to DEC205 Drives EBV-Protective Immunity in a Spontaneous Model of EBV-Driven Lymphoproliferative Disease

by Elshafa Hassan Ahmed, Eric Brooks, Shelby Sloan, Sarah Schlotter, Frankie Jeney, Claire Hale, Charlene Mao, Xiaoli Zhang, Eric McLaughlin, Polina Shindiapina, Salma Shire, Manjusri Das, Alexander Prouty, Gerard Lozanski, Admasu T. Mamuye, Tamrat Abebe, Lapo Alinari, Michael A. Caligiuri and Robert A. Baiocchi

Vaccines 2021, 9(6), 555; https://doi.org/10.3390/vaccines9060555 - 26 May 2021

Cited by 6 | Viewed by 3507

Abstract

Epstein-Barr virus (EBV) is a human herpes virus that infects over 90% of the world’s population and is linked to development of cancer. In immune-competent individuals, EBV infection is mitigated by a highly efficient virus-specific memory T-cell response. Risk of EBV-driven cancers increases with immune suppression (IS). EBV-seronegative recipients of solid organ transplants are at high risk of developing post-transplant lymphoproliferative disease (PTLD) due to iatrogenic IS. While reducing the level of IS may improve EBV-specific immunity and regression of PTLD, patients are at high risk for allograft rejection and need for immune-chemotherapy. Strategies to prevent PTLD in this vulnerable patient population represents an unmet need. We have previously shown that BZLF1-specific cytotoxic T-cell (CTL) expansion following reduced IS correlated with immune-mediated PTLD regression and improved patient survival. We have developed a vaccine to bolster EBV-specific immunity to the BZLF1 protein and show that co-culture of dendritic cells (DCs) loaded with a αDEC205-BZLF1 fusion protein with peripheral blood mononuclear cells (PMBCs) leads to expansion and increased cytotoxic activity of central-effector memory CTLs against EBV-transformed B-cells. Human–murine chimeric Hu-PBL-SCID mice were vaccinated with DCs loaded with αDEC205-BZLF1 or control to assess prevention of fatal human EBV lymphoproliferative disease. Despite a profoundly immunosuppressive environment, vaccination with αDEC205-BZLF1 stimulated clonal expansion of antigen-specific T-cells that produced abundant IFNγ and significantly prolonged survival. These results support preclinical and clinical development of vaccine approaches using BZLF1 as an immunogen to harness adaptive cellular responses and prevent PTLD in vulnerable patient populations. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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13 pages, 1754 KiB

Open AccessArticle

A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families

by Jie Wang, Katarzyna Urbanska, Prannda Sharma, Reza Nejati, Lauren Shaw, Megan S. Lim, Stephen J. Schuster and Daniel J. Powell Jr.

Vaccines 2020, 8(4), 631; https://doi.org/10.3390/vaccines8040631 - 31 Oct 2020

Cited by 2 | Viewed by 2876

Abstract

Peripheral T cell lymphomas (PTCLs) are generally chemotherapy resistant and have a poor prognosis. The lack of targeted immunotherapeutic approaches for T cell malignancies results in part from potential risks associated with targeting broadly expressed T cell markers, namely T cell depletion and clinically significant immune compromise. The knowledge that the T cell receptor (TCR) β chain in human α/β TCRs are grouped into Vβ families that can each be targeted by a monoclonal antibody can therefore be exploited for therapeutic purposes. Here, we develop a flexible approach for targeting TCR Vβ families by engineering T cells to express a chimeric CD64 protein that acts as a high affinity immune receptor (IR). We found that CD64 IR-modified T cells can be redirected with precision to T cell targets expressing selected Vβ families by combining CD64 IR-modified T cells with a monoclonal antibody directed toward a specific TCR Vβ family in vitro and in vivo. These findings provide proof of concept that TCR Vβ-family-specific T cell lysis can be achieved using this novel combination cell–antibody platform and illuminates a path toward high precision targeting of T cell malignancies without substantial immune compromise. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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Review

Jump to: Editorial, Research

28 pages, 8504 KiB

Open AccessReview

Bispecific Antibodies: A Smart Arsenal for Cancer Immunotherapies

by Gihoon You, Jonghwa Won, Yangsoon Lee, Dain Moon, Yunji Park, Sang Hoon Lee and Seung-Woo Lee

Vaccines 2021, 9(7), 724; https://doi.org/10.3390/vaccines9070724 - 2 Jul 2021

Cited by 32 | Viewed by 13167

Abstract

Following the clinical success of cancer immunotherapies such as immune checkpoint inhibitors blocking B7/CTLA-4 or PD-1/PD-L1 signaling and ongoing numerous combination therapies in the clinic,3 bispecific antibodies (BsAbs) are now emerging as a growing class of immunotherapies with the potential to improve clinical efficacy and safety further. Here, we describe four classes of BsAbs: (a) immune effector cell redirectors; (b) tumor-targeted immunomodulators; (c) dual immunomodulators; and (d) dual tumor-targeting BsAbs. This review describes each of these classes of BsAbs and presents examples of BsAbs in development. We reviewed the biological rationales and characteristics of BsAbs and summarized the current status and limitations of clinical development of BsAbs and strategies to overcome limitations. The field of BsAb-based cancer immunotherapy is growing, and more data from clinical trials are accumulating. Thus, BsAbs could be the next generation of new treatment options for cancer patients. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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24 pages, 1811 KiB

Open AccessReview

Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

by Li-Chung Chiu, Shu-Min Lin, Yu-Lun Lo, Scott Chih-Hsi Kuo, Cheng-Ta Yang and Ping-Chih Hsu

Vaccines 2021, 9(7), 689; https://doi.org/10.3390/vaccines9070689 - 23 Jun 2021

Cited by 12 | Viewed by 4169

Abstract

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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30 pages, 1030 KiB

Open AccessReview

Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

by Howard Donninger, Chi Li, John W. Eaton and Kavitha Yaddanapudi

Vaccines 2021, 9(6), 668; https://doi.org/10.3390/vaccines9060668 - 18 Jun 2021

Cited by 48 | Viewed by 6023

Abstract

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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15 pages, 688 KiB

Open AccessReview

Vaccines in Gastrointestinal Malignancies: From Prevention to Treatment

by Rani Chudasama, Quan Phung, Andrew Hsu and Khaldoun Almhanna

Vaccines 2021, 9(6), 647; https://doi.org/10.3390/vaccines9060647 - 13 Jun 2021

Cited by 10 | Viewed by 4279

Abstract

Gastrointestinal (GI) malignancies are some of the most common and devastating malignancies and include colorectal, gastric, esophageal, hepatocellular, and pancreatic carcinomas, among others. Five-year survival rates for many of these malignancies remain low. The majority presents at an advanced stage with limited treatment options and poor overall survival. Treatment is advancing but not at the same speed as other malignancies. Chemotherapy and radiation treatments are still only partially effective in GI malignancies and cause significant side effects. Thus, there is an urgent need for novel strategies in the treatment of GI malignancies. Recently, immunotherapy and checkpoint inhibitors have entered as potential new therapeutic options for patients, and thus, cancer vaccines may play a major role in the future of treatment for these malignancies. Further advances in understanding the interaction between the tumor and immune system have led to the development of novel agents, such as cancer vaccines. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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19 pages, 1076 KiB

Open AccessReview

Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment

by Bailee H. Sliker and Paul M. Campbell

Vaccines 2021, 9(6), 634; https://doi.org/10.3390/vaccines9060634 - 10 Jun 2021

Cited by 9 | Viewed by 3244

Abstract

Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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Graphical abstract

44 pages, 2830 KiB

Open AccessReview

Evolution of Cancer Vaccines—Challenges, Achievements, and Future Directions

by Ban Qi Tay, Quentin Wright, Rahul Ladwa, Christopher Perry, Graham Leggatt, Fiona Simpson, James W. Wells, Benedict J. Panizza, Ian H. Frazer and Jazmina L. G. Cruz

Vaccines 2021, 9(5), 535; https://doi.org/10.3390/vaccines9050535 - 20 May 2021

Cited by 45 | Viewed by 9932

Abstract

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient’s autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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20 pages, 603 KiB

Open AccessReview

Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

by Benjamin Wolfson, S. Elizabeth Franks and James W. Hodge

Vaccines 2021, 9(5), 509; https://doi.org/10.3390/vaccines9050509 - 15 May 2021

Cited by 17 | Viewed by 3323

Abstract

Effective treatment of established tumors requires rational multicombination immunotherapy strategies designed to target all functions of the patient immune system and tumor immune microenvironment. While these combinations build on the foundation of successful immune checkpoint blockade antibodies, it is increasingly apparent that successful immunotherapy will also require a cancer vaccine backbone to engage the immune system, thereby ensuring that additional immuno-oncology agents will engage a tumor-specific immune response. This review summarizes ongoing clinical trials built upon the backbone of cancer vaccines and focusing on those clinical trials that utilize multicombination (3+) immuno-oncology agents. We examine combining cancer vaccines with multiple checkpoint blockade antibodies, novel multifunctional molecules, adoptive cell therapy and immune system agonists. These combinations and those yet to enter the clinic represent the future of cancer immunotherapy. With a cancer vaccine backbone, we are confident that current and coming generations of rationally designed multicombination immunotherapy can result in effective therapy of established tumors. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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19 pages, 2487 KiB

Open AccessReview

Electroporation as the Immunotherapy Strategy for Cancer in Veterinary Medicine: State of the Art in Latin America

by Felipe Maglietti, Matías Tellado, Mariangela De Robertis, Sebastián Michinski, Juan Fernández, Emanuela Signori and Guillermo Marshall

Vaccines 2020, 8(3), 537; https://doi.org/10.3390/vaccines8030537 - 17 Sep 2020

Cited by 19 | Viewed by 6288

Abstract

Electroporation is a technology that increases cell membrane permeability by the application of electric pulses. Electrochemotherapy (ECT), the best-known application of electroporation, is a very effective local treatment for tumors of any histology in human and veterinary medicine. It induces a local yet robust immune response that is responsible for its high effectiveness. Gene electrotransfer (GET), used in research to produce a systemic immune response against cancer, is another electroporation-based treatment that is very appealing for its effectiveness, low cost, and simplicity. In this review, we present the immune effect of electroporation-based treatments and analyze the results of the vast majority of the published papers related to immune response enhancement by gene electrotransfer in companion animals with spontaneous tumors. In addition, we present a brief history of the initial steps and the state of the art of the electroporation-based treatments in Latin America. They have the potential to become an essential form of immunotherapy in the region. This review gives insight into the subject and helps to choose promising research lines for future work; it also helps to select the adequate treatment parameters for performing a successful application of this technology. Full article

(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment)

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