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Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances
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Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 18686

Special Issue Editor

Dr. Jacob J Adashek

E-Mail Website
Guest Editor
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, MD, USA
Interests: precision medicine; developmental therapeutics; biomarker-driven trials

Special Issue Information

Dear Colleagues,

The treatment landscape for many cancers is rapidly evolving with the advent of immune checkpoint inhibitors and multi-omics. Combining the insights of next-generation sequencing along with transcriptomic and immunomic data can often inform treatment decision making for some cancers. In certain circumstances the use of immune checkpoint inhibitors has led to dramatic responses in various tumor types. Understanding which patients may yield the most benefit from these agents is of the utmost importance and interest of the greater oncology community. Deciphering how to hijack this response for patients who do not have such responses is also important and of interest.  Various groups have led and continue to lead efforts into combining immune checkpoint in combination with various targeted therapies in efforts to improve responses to these agents. Additionally, there is an abundance of ongoing clinical trials to investigate novel checkpoints including but not limited to LAG-3, TIM3, TIGIT, and many more. Identifying which patients may have the most clinical benefit from these agents and how to predict which patients may have this benefit is part of the ongoing effort of the development of these agents. In this Special Issue, we aim to draw together research from experts in the field that highlight immunotherapeutic agents and strategies, and identify future directions that will lead to discoveries and therapies for these drugs in patients with cancer.

Dr. Jacob J Adashek
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.

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. Pharmaceuticals 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 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

  • immune checkpoint inhibitor
  • biomarker-driven trials
  • genomics
  • immunomics
  • precision medicine
  • multiomics

Published Papers (6 papers)

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Research

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10 pages, 695 KiB  
Article
Response to Anti-PD1/L1 Antibodies in Advanced Urothelial Cancer in the ‘Real-Life’ Setting
by Moran Gadot, Ido Arad, Eshetu G. Atenafu, Meital Levartovsky, Orith Portnoy, Tima Davidson, Rachel Schor-Bardach, Raanan Berger and Raya Leibowitz
Pharmaceuticals 2022, 15(9), 1154; https://doi.org/10.3390/ph15091154 - 16 Sep 2022
Viewed by 1492
Abstract
Immune checkpoint inhibitors (ICIs) are now the standard of care for metastatic urothelial carcinoma (mUC) patients. Our aim was to describe the activity of ICIs in mUC and find the clinical parameters associated with response. This is a retrospective, single-center chart review of [...] Read more.
Immune checkpoint inhibitors (ICIs) are now the standard of care for metastatic urothelial carcinoma (mUC) patients. Our aim was to describe the activity of ICIs in mUC and find the clinical parameters associated with response. This is a retrospective, single-center chart review of mUC patients receiving ICIs. The overall survival (OS) was plotted using the Kaplan–Meier method and was compared using a log-rank test. Associations between the variables and responses were analyzed by univariate and multivariable analyses, using either logistic regression or a Chi-square/Fisher’s exact test. Ninety-four patients received ICIs, 85% of which were in the second line or beyond; the median age was 71.8 years, and 82% were men. Six (6.4%), 11 (11.7%), 7 (7.4%) and 70 (74.5%) patients achieved a complete response (CR), partial response (PR), mixed response/stable disease (M/SD) or progressive disease (PD), respectively. The median overall survival was 3.2 months for the entire cohort and was significantly different according to the response pattern—not reached, 32.3, 6.4 and 2.0 months for CR, PR, M/SD and PD, respectively. The response was not significantly associated with the line of treatment. ‘Site of metastasis’ was associated with the response, and the absolute neutrophil count was borderline associated with the response. In summary, we found a substantial variance in the potential benefit from ICIs in mUC, emphasizing the need for predictive biomarkers and frequent monitoring of mUC patients receiving ICIs. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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Review

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17 pages, 1023 KiB  
Review
Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review
by Atulya Aman Khosla, Karan Jatwani, Rohit Singh, Aswanth Reddy, Ishmael Jaiyesimi and Aakash Desai
Pharmaceuticals 2023, 16(10), 1461; https://doi.org/10.3390/ph16101461 - 14 Oct 2023
Cited by 1 | Viewed by 3675
Abstract
Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with [...] Read more.
Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies. Additionally, the challenges and opportunities associated with their use in the clinic are discussed, along with future directions for research and development in this exciting area of cancer immunotherapy. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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27 pages, 859 KiB  
Review
The Role of Immune Checkpoint Inhibitors in Metastatic Pancreatic Cancer: Current State and Outlook
by Linh Chi Tran, Berna C. Özdemir and Martin D. Berger
Pharmaceuticals 2023, 16(10), 1411; https://doi.org/10.3390/ph16101411 - 04 Oct 2023
Cited by 2 | Viewed by 1830
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, characterized by its aggressive tumor biology and poor prognosis. While immune checkpoint inhibitors (ICIs) play a major part in the treatment algorithm of various solid tumors, there is still no evidence of clinical [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, characterized by its aggressive tumor biology and poor prognosis. While immune checkpoint inhibitors (ICIs) play a major part in the treatment algorithm of various solid tumors, there is still no evidence of clinical benefit from ICI in patients with metastatic PDAC (mPDAC). This might be due to several reasons, such as the inherent low immunogenicity of pancreatic cancer, the dense stroma-rich tumor microenvironment that precludes an efficient migration of antitumoral effector T cells to the cancer cells, and the increased proportion of immunosuppressive immune cells, such as regulatory T cells (Tregs), cancer-associated fibroblasts (CAFs), and myeloid-derived suppressor cells (MDSCs), facilitating tumor growth and invasion. In this review, we provide an overview of the current state of ICIs in mPDAC, report on the biological rationale to implement ICIs into the treatment strategy of pancreatic cancer, and discuss preclinical studies and clinical trials in this field. Additionally, we shed light on the challenges of implementing ICIs into the treatment strategy of PDAC and discuss potential future directions. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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24 pages, 1363 KiB  
Review
Agnostic Approvals in Oncology: Getting the Right Drug to the Right Patient with the Right Genomics
by Valentina Tateo, Paola Valeria Marchese, Veronica Mollica, Francesco Massari, Razelle Kurzrock and Jacob J. Adashek
Pharmaceuticals 2023, 16(4), 614; https://doi.org/10.3390/ph16040614 - 19 Apr 2023
Cited by 19 | Viewed by 6222
Abstract
(1) Background: The oncology field has drastically changed with the advent of precision medicine, led by the discovery of druggable genes or immune targets assessed through next-generation sequencing. Biomarker-based treatments are increasingly emerging, and currently, six tissue-agnostic therapies are FDA-approved. (2) Methods: We [...] Read more.
(1) Background: The oncology field has drastically changed with the advent of precision medicine, led by the discovery of druggable genes or immune targets assessed through next-generation sequencing. Biomarker-based treatments are increasingly emerging, and currently, six tissue-agnostic therapies are FDA-approved. (2) Methods: We performed a review of the literature and reported the trials that led to the approval of tissue-agnostic treatments and ongoing clinical trials currently investigating novel biomarker-based approaches. (3) Results: We discussed the approval of agnostic treatments: pembrolizumab and dostarlimab for MMRd/MSI-H, pembrolizumab for TMB-H, larotrectinib and entrectinib for NTRK-fusions, dabrafenib plus trametinib for BRAF V600E mutation, and selpercatinib for RET fusions. In addition, we reported novel clinical trials of biomarker-based approaches, including ALK, HER2, FGFR, and NRG1. (4) Conclusions: Precision medicine is constantly evolving, and with the improvement of diagnostic tools that allow a wider genomic definition of the tumor, tissue-agnostic targeted therapies are a promising treatment strategy tailored to the specific tumor genomic profile, leading to improved survival outcomes. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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23 pages, 874 KiB  
Review
Checkpoint Inhibitor-Associated Scleroderma and Scleroderma Mimics
by Michael Macklin, Sudeep Yadav, Reem Jan and Pankti Reid
Pharmaceuticals 2023, 16(2), 259; https://doi.org/10.3390/ph16020259 - 08 Feb 2023
Cited by 6 | Viewed by 2538
Abstract
Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of [...] Read more.
Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of data regarding ICI-associated scleroderma which can carry significant morbidity and limit the ability to continue effective ICI therapy. Our review aimed to analyze the current literature on ICI-associated systemic scleroderma (ICI-SSc) and key scleroderma mimics. Cases of ICI-SSc had notable differences from primary SSc, such as fewer vascular features and less seropositivity (such as scleroderma-specific antibodies and antinuclear antibodies). We found that patients with a diagnosis of SSc prior to the start of ICI can also experience flares of pre-existing disease after ICI treatment used for their cancer. Regarding scleroderma mimics, several cases of ICI-eosinophilic fasciitis have also been described with variable clinical presentations and courses. We found no cases of scleroderma mimics: ICI-scleromyxedema or ICI-scleroedema. There is a critical need for multi-institutional efforts to collaborate on developing a patient database and conducting robust, prospective research on ICI-scleroderma. This will ultimately facilitate more effective clinical evaluations and management for ICI-scleroderma. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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13 pages, 292 KiB  
Review
Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer
by Ivy Riano, Inas Abuali, Aditya Sharma, Jewelia Durant and Konstantin H. Dragnev
Pharmaceuticals 2023, 16(2), 233; https://doi.org/10.3390/ph16020233 - 03 Feb 2023
Cited by 1 | Viewed by 2014
Abstract
The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies [...] Read more.
The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/− radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor in Cancer Therapy: Recent Advances)
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