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.

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

2021 ◽  
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 neo-plasms. 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 pre-clinical 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.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors

2020 ◽  
Vol 21 (23) ◽  
pp. 9056
Author(s):  
Valentina Tateo ◽  
Lisa Manuzzi ◽  
Andrea De Giglio ◽  
Claudia Parisi ◽  
Giuseppe Lamberti ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Cancer Biology ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
New Treatment ◽  
Light Side ◽  
Thoracic Malignancies

Thymic epithelial tumors (TETs) are a group of rare thoracic malignancies, including thymic carcinomas (TC) and thymomas (Tm). Autoimmune paraneoplastic diseases are often observed in TETs, especially Tms. To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory TETs. In the last few years, the deepening of knowledge on thymus’ immunobiology and involved altered genetic pathways have laid the foundation for new treatment options in these rare neoplasms. Recently, the immunotherapy revolution has landed in TETs, showing both a dark and light side. Indeed, despite the survival benefit, the occurrence of severe autoimmune treatment-related adverse events has risen crescent uncertainty about the feasibility of immunotherapy in these patients, prone to autoimmunity for their cancer biology. In this review, after summarizing immunobiology and immunopathology of TETs, we discuss available data on immune-checkpoint inhibitors and future perspectives of this therapeutic strategy.

PIVOT-10: A phase II study of bempegaldesleukin (NKTR-214) in combination with nivolumab (NIVO) in cisplatin (cis) ineligible patients with previously untreated locally advanced or metastatic urothelial cancer (mUC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS589-TPS589
Author(s):  
Robert A. Huddart ◽  
Arlene O. Siefker-Radtke ◽  
Arjun Vasant Balar ◽  
Mehmet Asim Bilen ◽  
Thomas Powles ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Objective Response ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Phase 2 ◽  
Metastatic Urothelial Cancer ◽  
Evaluable Population ◽  
Duration Of Response ◽  
New Treatment

TPS589 Background: Checkpoint inhibitors can achieve durable responses in cis-ineligible 1L mUC. However, use is restricted to patients whose tumors are PD-L1 high. Approximately 70% of cis-ineligible patients have tumors with low PD-L1 expression, leaving a significant proportion of 1L mUC patients in need of new treatment options. Bempegaldesleukin (BEMPEG; NKTR-214) is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor. NIVO is an anti-PD-1 antibody that is approved for treatment in several types of cancers, including 2L mUC after treatment with a platinum agent. Early BEMPEG plus NIVO data in 1L mUC (cis-eligible and -ineligible) patients found an objective response rate (ORR) of 48% (13/27) in the efficacy evaluable population (defined as having undergone at least one post-baseline scan) and a CR rate of 19%, prompting this further exploration of BEMPEG plus NIVO in a phase 2 study (Siefker-Radke, 2019). Methods: This Phase 2 multi-national trial evaluates BEMPEG plus NIVO in previously untreated patients with cis-ineligible mUC. Eligibility also requires tumor tissue be analyzed by central laboratory to document PD-L1 status. Approximately 205 patients will be enrolled. BEMPEG (0.006 mg/kg) and NIVO (360 mg) are given intravenously (IV) on Day 1 of each 3-week cycle. The primary endpoint is ORR assessed per RECIST 1.1 by blinded independent central review (BICR) in patients with low PD-L1 expression (defined as Combined Positive Score [CPS] < 10). Secondary endpoints include ORR and duration of response in all treated patients, safety, and tolerability. Tumor and blood samples will be collected for biomarker analyses. Enrollment is ongoing. Clinical trial information: NCT03785925.

New Treatment Options in Advanced Squamous Cell Lung Cancer

2019 ◽  
pp. e198-e206 ◽  
Author(s):  
Paul K. Paik ◽  
Rathi Narayana Pillai ◽  
Christopher S. Lathan ◽  
Sylvia A. Velasco ◽  
Vassiliki Papadimitrakopoulou
Keyword(s):  
Squamous Cell ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Substantial Improvement ◽  
Lung Cancers ◽  
The Past ◽  
New Treatment ◽  
Line Setting ◽  
Rapid Shift

The past few years have witnessed a rapid shift in the treatments for patients with squamous cell lung cancers (SQCLCs) after the U.S. Food and Drug Administration approval of a number of immune checkpoint inhibitors as second-line therapies for patients with non–small cell lung cancers. These series of approvals marked the first substantial improvement in overall survival for patients with SQCLC in over a decade. Further gains have been made more recently with the incorporation of immune checkpoint inhibition in the first-line setting, either as monotherapy or in combination with chemotherapy. These advances have, however, exposed existing deficiencies in the management of this disease. Despite a deeper understanding of the genomic alterations that characterize SQCLCs and years of trial work targeting these alterations, personalized therapies remain out of hand. Future studies will continue to focus on identifying targeted approaches to expand the treatment options for our patients.

scholarly journals The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 529 ◽  
Author(s):  
Benjamin Gordon ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
New Combination ◽  
Breast Carcinomas ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
Disseminated Disease

Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome.

scholarly journals Bispecific Antibodies: A Smart Arsenal for Cancer Immunotherapies

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 724
Author(s):  
Gihoon You ◽  
Jonghwa Won ◽  
Yangsoon Lee ◽  
Dain Moon ◽  
Yunji Park ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Treatment Options ◽  
Bispecific Antibodies ◽  
Current Status ◽  
Combination Therapies ◽  
Immune Effector ◽  
New Treatment ◽  
Cancer Immunotherapies

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.

scholarly journals Combining Cancer Vaccines with Immunotherapy: Establishing a New Immunological Approach

2021 ◽  
Vol 22 (15) ◽  
pp. 8035
Author(s):  
Chang Gon Kim ◽  
Yun Beom Sang ◽  
Ji Hyun Lee ◽  
Hong Jae Chon
Keyword(s):  
Cancer Vaccines ◽  
Vaccine Development ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanisms ◽  
Antigen Delivery ◽  
Vaccine Platform ◽  
Personalized Cancer ◽  
Therapeutic Cancer Vaccines ◽  
Antigen Repertoire

Therapeutic cancer vaccines have become increasingly qualified for use in personalized cancer immunotherapy. A deeper understanding of tumor immunology and novel antigen delivery technologies has assisted in optimizing vaccine design. Therapeutic cancer vaccines aim to establish long-lasting immunological memory against tumor cells, thereby leading to effective tumor regression and minimizing non-specific or adverse events. However, due to several resistance mechanisms, significant challenges remain to be solved in order to achieve these goals. In this review, we describe our current understanding with respect to the use of the antigen repertoire in vaccine platform development. We also summarize various intrinsic and extrinsic resistance mechanisms behind the failure of cancer vaccine development in the past. Finally, we suggest a strategy that combines immune checkpoint inhibitors to enhance the efficacy of cancer vaccines.

scholarly journals Insights into Potential Pathogenesis and Treatment Options for Immune-Checkpoint Inhibitor-Related Pneumonitis

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1484
Author(s):  
Hiroyuki Ando ◽  
Kunihiro Suzuki ◽  
Toyoshi Yanagihara
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Frequent Adverse Event ◽  
Programmed Cell Death 1 ◽  
New Treatment

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed cell death-1-ligand 1 (PD-L1) have become new treatment options for various malignancies. ICIs bind to immune-checkpoint inhibitory receptors or to the foregoing ligands and block inhibitory signals to release the brakes on the immune system, thereby enhancing immune anti-tumor responses. On the other hand, unlike conventional chemotherapies, ICIs can cause specific side effects, called immune-related adverse events (irAEs). These toxicities may affect various organs, including the lungs. ICI-related pneumonitis (ICI-pneumonitis) is not the most frequent adverse event, but it is serious and can be fatal. In this review, we summarize recent findings regarding ICI-pneumonitis, with a focus on potential pathogenesis and treatment.

scholarly journals Gastric and Esophageal Cancers: Guidelines Updates

2021 ◽  
Vol 19 (5.5) ◽  
pp. 639-643
Author(s):  
Crystal S. Denlinger ◽  
Kristina A. Matkowskyj ◽  
Mary F. Mulcahy
Keyword(s):  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Esophageal Cancers ◽  
New Treatment

For the treatment of gastric and esophageal cancers, several pivotal trials—especially those evaluating immune checkpoint inhibitors (ICIs)—have altered the treatment landscape and led to changes in the NCCN Guidelines. In addition to pembrolizumab and nivolumab, new treatment options include trastuzumab-deruxtecan (T-DXd), ramucirumab, and trifluridine/tipiracil. These agents convey varying degrees of benefit depending on treatment line, PD-L1 expression, HER2 expression, and tumor histology. Recently, ICIs have been incorporated into the first-line treatment of HER2-negative advanced esophageal, gastroesophageal junction (GEJ), and gastric cancers, in addition to second-line treatment of advanced esophageal and GEJ cancer of squamous histology. T-DXd is another new second-line option for HER2-positive esophageal, GEJ, and gastric adenocarcinomas. ICIs are now moving into the adjuvant setting as well, and a new recommendation is nivolumab use after preoperative chemoradiation and surgery in patients who have residual disease identified at the time of their R0 resections.

Sign in / Sign up

Export Citation Format

Share Document