scholarly journals Immunotherapies and Combination Strategies for Immuno-Oncology

2020 ◽  
Vol 21 (14) ◽  
pp. 5009 ◽  
Author(s):  
Cody Barbari ◽  
Tyler Fontaine ◽  
Priyanka Parajuli ◽  
Narottam Lamichhane ◽  
Silvia Jakubski ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Vaccines ◽  
Checkpoint Inhibition ◽  
Cancer Treatments ◽  
Cell Therapies ◽  
Combination Treatments ◽  
Combination Strategies ◽  
Recent Developments ◽  
Traditional Therapies ◽  
Cancerous Cells

The advent of novel immunotherapies in the treatment of cancers has dramatically changed the landscape of the oncology field. Recent developments in checkpoint inhibition therapies, tumor-infiltrating lymphocyte therapies, chimeric antigen receptor T cell therapies, and cancer vaccines have shown immense promise for significant advancements in cancer treatments. Immunotherapies act on distinct steps of immune response to augment the body’s natural ability to recognize, target, and destroy cancerous cells. Combination treatments with immunotherapies and other modalities intend to activate immune response, decrease immunosuppression, and target signaling and resistance pathways to offer a more durable, long-lasting treatment compared to traditional therapies and immunotherapies as monotherapies for cancers. This review aims to briefly describe the rationale, mechanisms of action, and clinical efficacy of common immunotherapies and highlight promising combination strategies currently approved or under clinical development. Additionally, we will discuss the benefits and limitations of these immunotherapy approaches as monotherapies as well as in combination with other treatments.

scholarly journals Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2761
Author(s):  
Annalisa Chianese ◽  
Biagio Santella ◽  
Annalisa Ambrosino ◽  
Debora Stelitano ◽  
Luca Rinaldi ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Entry ◽  
Therapeutic Option ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Tumor Treatment ◽  
Therapeutic Approaches ◽  
Combination Treatments ◽  
Combination Strategies ◽  
Current Therapies

According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).

Immunotherapy in cancer: mechanisms of immune response and their place in cancer treatments

2017 ◽  
Vol 1 (38) ◽  
Author(s):  
Dana Lucia Stănculeanu ◽  
Carmen Ardeleanu ◽  
Daniela Zob ◽  
Raluca Ioana Mihăilă ◽  
Oana Cătălina Toma ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Treatments

scholarly journals Myelopoiesis during Solid Cancers and Strategies for Immunotherapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 968
Author(s):  
Tyler J. Wildes ◽  
Bayli DiVita Dean ◽  
Catherine T. Flores
Keyword(s):  
Myeloid Cells ◽  
Hematopoietic Stem ◽  
Cell Therapies ◽  
Broad Array ◽  
Stem And Progenitor Cells ◽  
Recent Developments ◽  
Immature Myeloid Cells ◽  
Significant Discovery ◽  
The Relationship ◽  
Clinical Advances

Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity has proven more difficult. The myeloid compartment, including macrophages, neutrophils, and dendritic cells, has a significant impact on the persistence or elimination of tumors. Myeloid cells, specifically in the tumor microenvironment, have direct contact with tumor tissue and coordinate with tumor-reactive T cells to either stimulate or antagonize cancer immunity. However, the myeloid compartment comprises a broad array of cells in various stages of development. In addition, hematopoietic stem and progenitor cells at various stages of myelopoiesis in distant sites undergo significant modulation by tumors. Understanding how tumors exert their influence on myeloid progenitors is critical to making clinically meaningful improvements in these pathways. Therefore, this review will cover recent developments in our understanding of how solid tumors modulate myelopoiesis to promote the formation of pro-tumor immature myeloid cells. Then, it will cover some of the potential avenues for capitalizing on these mechanisms to generate antitumor immunity.

scholarly journals Cancer Vaccines for Genitourinary Tumors: Recent Progresses and Future Possibilities

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 623
Author(s):  
Brigida Anna Maiorano ◽  
Giovanni Schinzari ◽  
Davide Ciardiello ◽  
Maria Grazia Rodriquenz ◽  
Antonio Cisternino ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Viral Vectors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Tumor Development ◽  
Resistance Mechanisms ◽  
High Morbidity ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
New Treatment

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neoplasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched PubMed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further preclinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

Understanding relevant immune mechanisms in gastrointestinal oncology

2021 ◽  
pp. 107815522199286
Author(s):  
Bulent Cetin ◽  
Ozge Gumusay
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Gastrointestinal Cancers ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Multiple Treatment ◽  
Gi Cancers ◽  
The Many

Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.

scholarly journals Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander J. Stephens ◽  
Nicola A. Burgess-Brown ◽  
Shisong Jiang
Keyword(s):  
Cancer Vaccines ◽  
Adaptive Immune Response ◽  
Comprehensive Treatment ◽  
Vaccine Strategy ◽  
Cancer Treatments ◽  
Cross Presentation ◽  
Peptide Antigens ◽  
Overall Design ◽  
Peptide Derivatives ◽  
Antigen Presenting

Peptide-based cancer vaccines rely upon the strong activation of the adaptive immune response to elicit its effector function. They have shown to be highly specific and safe, but have yet to prove themselves as an efficacious treatment for cancer in the clinic. This is for a variety of reasons, including tumour heterogeneity, self-tolerance, and immune suppression. Importance has been placed on the overall design of peptide-based cancer vaccines, which have evolved from simple peptide derivatives of a cancer antigen, to complex drugs; incorporating overlapping regions, conjugates, and delivery systems to target and stimulate different components of antigen presenting cells, and to bolster antigen cross-presentation. Peptide-based cancer vaccines are increasingly becoming more personalised to an individual’s tumour antigen repertoire and are often combined with existing cancer treatments. This strategy ultimately aids in combating the shortcomings of a more generalised vaccine strategy and provides a comprehensive treatment, taking into consideration cancer cell variability and its ability to avoid immune interrogation.

scholarly journals Breast Cancer Immunotherapy: An Update

2018 ◽  
Vol 12 ◽  
pp. 117822341877480 ◽  
Author(s):  
Issam Makhoul ◽  
Mohammad Atiq ◽  
Ahmed Alwbari ◽  
Thomas Kieber-Emmons
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Cancer Surveillance ◽  
Cancer Disease ◽  
Immune Attack

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

scholarly journals Dendritic Cell-Based and Other Vaccination Strategies for Pediatric Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1396 ◽  
Author(s):  
Sévérine de Bruijn ◽  
Sébastien Anguille ◽  
Joris Verlooy ◽  
Evelien L. Smits ◽  
Viggo F. van Tendeloo ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Pediatric Cancer ◽  
Cancer Vaccines ◽  
Pediatric Population ◽  
Cancer Recurrence ◽  
Western World ◽  
Cancer Treatments ◽  
Vaccination Strategies ◽  
Vulnerable Patient ◽  
Therapeutic Cancer Vaccines

Dendritic cell-based and other vaccination strategies that use the patient’s own immune system for the treatment of cancer are gaining momentum. Most studies of therapeutic cancer vaccination have been performed in adults. However, since cancer is one of the leading causes of death among children past infancy in the Western world, the hope is that this form of active specific immunotherapy can play an important role in the pediatric population as well. Since children have more vigorous and adaptable immune systems than adults, therapeutic cancer vaccines are expected to have a better chance of creating protective immunity and preventing cancer recurrence in pediatric patients. Moreover, in contrast to conventional cancer treatments such as chemotherapy, therapeutic cancer vaccines are designed to specifically target tumor cells and not healthy cells or tissues. This reduces the likelihood of side effects, which is an important asset in this vulnerable patient population. In this review, we present an overview of the different therapeutic cancer vaccines that have been studied in the pediatric population, with a main focus on dendritic cell-based strategies. In addition, new approaches that are currently being investigated in clinical trials are discussed to provide guidance for further improvement and optimization of pediatric cancer vaccines.

The Complex Cancer Care Coverage Environment — What is the Role of Legislation?

2020 ◽  
Vol 48 (3) ◽  
pp. 538-551 ◽  
Author(s):  
Christine Leopold ◽  
Rebecca L. Haffajee ◽  
Christine Y. Lu ◽  
Anita K. Wagner
Keyword(s):  
Cancer Care ◽  
Insurance Coverage ◽  
Cancer Therapeutics ◽  
Health Insurance Coverage ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Difficult Situation ◽  
Cell Therapies ◽  
State Laws ◽  
Anti Cancer

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates.

scholarly journals RNA Transcription and Splicing Errors as a Source of Cancer Frameshift Neoantigens for Vaccines

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luhui Shen ◽  
Jian Zhang ◽  
HoJoon Lee ◽  
Milene Tavares Batista ◽  
Stephen Albert Johnston
Keyword(s):  
Immune Response ◽  
Cancer Therapy ◽  
Antibody Response ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Peptide Array ◽  
Rna Transcription ◽  
Dna Mutations ◽  
Tumor Dna

Abstract The success of checkpoint inhibitors in cancer therapy is largely attributed to activating the patient’s immune response to their tumor’s neoantigens arising from DNA mutations. This realization has motivated the interest in personal cancer vaccines based on sequencing the patient’s tumor DNA to discover neoantigens. Here we propose an additional, unrecognized source of tumor neoantigens. We show that errors in transcription of microsatellites (MS) and mis-splicing of exons create highly immunogenic frameshift (FS) neoantigens in tumors. The sequence of these FS neoantigens are predictable, allowing creation of a peptide array representing all possible neoantigen FS peptides. This array can be used to detect the antibody response in a patient to the FS peptides. A survey of 5 types of cancers reveals peptides that are personally reactive for each patient. This source of neoantigens and the method to discover them may be useful in developing cancer vaccines.

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