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Cancer Immunotherapies

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2016) | Viewed by 127980

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Special Issue Editor

Dr. Vita Golubovskaya

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Guest Editor

1. Research and Business Development, Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA
2. Department of Medicine, University of Oklahoma, Oklahoma City, OK 73126, USA
Interests: Immunotherapy; CAR-T cells; tumor microenvironment; checkpoint protein; hypoxia; tumor survival signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer immunotherapy (therapy that uses a person's immune system to fight cancer) has become an important field of oncology. There are four main types of immunotherapies: monoclonal antibodies; cancer vaccines; checkpoint inhibitors; and non-specific cancer immunotherapies (therapies that do not target cancer specifically, but stimulate immune cells that can lead to anti-cancer immune response, such as interleukins, cytokines, interferons, and others). Tumors express ligands to immune checkpoint proteins, such as PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), mediating block of immune response. Thus, the development of inhibitors of these immune checkpoint pathways is a promising area of immune therapeutics. In addition, tumors express tumor antigens that can be targeted with antibodies; antibody-drug conjugates; chimeric antigen receptor (CAR) T cells; or by other approaches. Dendritic cell vaccine is another important immunotherapy approach against cancer. This Special Issue is focused on recent immunotherapy approaches, novel immune therapeutics, and immunology signaling pathways in cancer.

Dr. Vita Golubovskaya
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.

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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 2900 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
CAR-T cell
dendritic cell
lymphocyte
tumor antigen
monoclonal antibody

Published Papers (11 papers)

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Research

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1479 KiB

Open AccessArticle

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

by Vincent K. Tuohy, Ritika Jaini, Justin M. Johnson, Matthew G. Loya, Dennis Wilk, Erinn Downs-Kelly and Suparna Mazumder

Cancers 2016, 8(6), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8060056 - 16 Jun 2016

Cited by 22 | Viewed by 9218

Abstract

We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC)—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessArticle

A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission

by Roisin E. O’Cearbhaill, Govind Ragupathi, Jianglong Zhu, Qian Wan, Svetlana Mironov, Guangbin Yang, Maria K. Spassova, Alexia Iasonos, Sara Kravetz, Ouathek Ouerfelli, David R. Spriggs, Samuel J. Danishefsky and Paul J. Sabbatini

Cancers 2016, 8(4), 46; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8040046 - 22 Apr 2016

Cited by 32 | Viewed by 7710

Abstract

We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011–Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient’s pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36–68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2–39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Review

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208 KiB

Open AccessReview

Immunotherapy for Colorectal Cancer

by Patrick M. Boland and Wen Wee Ma

Cancers 2017, 9(5), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers9050050 - 11 May 2017

Cited by 122 | Viewed by 13520

Abstract

The recent success of anti-PD1 drugs in metastatic colorectal cancer patients with mismatch repair deficiency generated overwhelming enthusiasm for immunotherapy in the disease. However, patients with mismatch repair deficient colorectal cancer represent only a small subset of the metastatic population. Current research focuses on advancing immunotherapy to earlier stages of the disease including adjuvant and first-line metastatic settings, and on inducing sensitivity to immune checkpoint inhibitor therapy through a combinatorial approach. Here, we review the contemporary understanding of the immune and molecular landscape in colorectal cancer and discuss ongoing clinical trials evaluating novel combination regimens based on immune checkpoint inhibitors. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessReview

Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions

by Shilpa Gupta, David Gill, Austin Poole and Neeraj Agarwal

Cancers 2017, 9(2), 15; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers9020015 - 27 Jan 2017

Cited by 35 | Viewed by 10193

Abstract

Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessFeature PaperReview

Advances in Cancer Immunotherapy in Solid Tumors

by Smitha Menon, Sarah Shin and Grace Dy

Cancers 2016, 8(12), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8120106 - 24 Nov 2016

Cited by 122 | Viewed by 12541

Abstract

Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessReview

Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma

by Darrin V. Bann, Daniel G. Deschler and Neerav Goyal

Cancers 2016, 8(10), 87; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8100087 - 22 Sep 2016

Cited by 22 | Viewed by 6787

Abstract

The immune system plays a key role in preventing tumor formation by recognizing and destroying malignant cells. For over a century, researchers have attempted to harness the immune response as a cancer treatment, although this approach has only recently achieved clinical success. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is associated with cigarette smoking, alcohol consumption, betel nut use, and human papillomavirus infection. Unfortunately, worldwide mortality from HNSCC remains high, partially due to limits on therapy secondary to the significant morbidity associated with current treatments. Therefore, immunotherapeutic approaches to HNSCC treatment are attractive for their potential to reduce morbidity while improving survival. However, the application of immunotherapies to this disease has been challenging because HNSCC is profoundly immunosuppressive, resulting in decreased absolute lymphocyte counts, impaired natural killer cell function, reduced antigen-presenting cell function, and a tumor-permissive cytokine profile. Despite these challenges, numerous clinical trials testing the safety and efficacy of immunotherapeutic approaches to HNSCC treatment are currently underway, many of which have produced promising results. This review will summarize immunotherapeutic approaches to HNSCC that are currently undergoing clinical trials. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessReview

Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy

by Anthony Visioni and Joseph Skitzki

Cancers 2016, 8(9), 86; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8090086 - 20 Sep 2016

Cited by 6 | Viewed by 5208

Abstract

A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessReview

CD8 T Cell–Independent Antitumor Response and Its Potential for Treatment of Malignant Gliomas

by Katherine A. Murphy and Thomas S. Griffith

Cancers 2016, 8(8), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8080071 - 27 Jul 2016

Cited by 6 | Viewed by 4428

Abstract

Malignant brain tumors continue to represent a devastating diagnosis with no real chance for cure. Despite an increasing list of potential salvage therapies, standard-of-care for these patients has not changed in over a decade. Immunotherapy has been seen as an exciting option, with the potential to offer specific and long lasting tumor clearance. The “gold standard” in immunotherapy has been the development of a tumor-specific CD8 T cell response to potentiate tumor clearance and immunological memory. While many advances have been made in the field of immunotherapy, few therapies have seen true success. Many of the same principles used to develop immunotherapy in tumors of the peripheral organs have been applied to brain tumor immunotherapy. The immune-specialized nature of the brain should call into question whether this approach is appropriate. Recent results from our own experiments require a rethinking of current dogma. Perhaps a CD8 T cell response is not sufficient for an organ as immunologically unique as the brain. Examination of previously elucidated principles of the brain’s immune-specialized status and known immunological preferences should generate discussion and experimentation to address the failure of current therapies. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessReview

A Perspective of Immunotherapy for Prostate Cancer

by Ida Silvestri, Susanna Cattarino, Sabrina Giantulli, Cristina Nazzari, Giulia Collalti and Alessandro Sciarra

Cancers 2016, 8(7), 64; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8070064 - 07 Jul 2016

Cited by 27 | Viewed by 7478

Abstract

In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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Open AccessFeature PaperReview

Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

by Vita Golubovskaya and Lijun Wu

Cancers 2016, 8(3), 36; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers8030036 - 15 Mar 2016

Cited by 367 | Viewed by 47541

Abstract

This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors. Full article

(This article belongs to the Special Issue Cancer Immunotherapies)

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