scholarly journals Safety and Efficacy of Therapeutic Cancer Vaccines Alone or in Combination With Immune Checkpoint Inhibitors in Cancer Treatment

2019 ◽  
Vol 10 ◽  
Author(s):  
Jing Zhao ◽  
Ye Chen ◽  
Zhen-Yu Ding ◽  
Ji-Yan Liu
Keyword(s):  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Safety And Efficacy ◽  
Therapeutic Cancer Vaccines

scholarly journals Safety and Efficacy of Personalized Cancer Vaccines in Combination With Immune Checkpoint Inhibitors in Cancer Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan-Yan Liao ◽  
Shuang Zhang
Keyword(s):  
Immune Checkpoint ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Treatment Modalities ◽  
Strong Immune Response ◽  
Safety And Efficacy ◽  
Central Tolerance ◽  
Personalized Cancer

Cancer immunotherapy can induce sustained responses in patients with cancers in a broad range of tissues, however, these treatments require the optimized combined therapeutic strategies. Despite immune checkpoint inhibitors (ICIs) have lasting clinical benefit, researchers are trying to combine them with other treatment modalities, and among them the combination with personalized cancer vaccines is attractive. Neoantigens, arising from mutations in cancer cells, can elicit strong immune response without central tolerance and out-target effects, which is a truly personalized method. Growing studies show that the combination can elevate the antitumor efficacy with acceptable safety and minimal additional toxicity compared with single agent vaccine or ICI. Herein, we have searched these preclinical and clinical trials and summarized safety and efficacy of personalized cancer vaccines combined with ICIs in several malignancies. Meanwhile, we discuss the rationale of the combination and future challenges.

scholarly journals Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Targeted Delivery ◽  
Cancer Vaccines ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Host Immune Responses ◽  
Near Future ◽  
Identification And Characterization

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8+ cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8+ T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.

scholarly journals Myocarditis Surveillance With High-Sensitivity Troponin I During Cancer Treatment With Immune Checkpoint Inhibitors

2021 ◽  
Vol 3 (1) ◽  
pp. 137-139
Author(s):  
Sarah Waliany ◽  
Joel W. Neal ◽  
Sunil Reddy ◽  
Heather Wakelee ◽  
Sumit A. Shah ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Checkpoint Inhibitors ◽  
High Sensitivity ◽  
High Sensitivity Troponin

Immune checkpoint inhibitors: Significant advancements in non–small cell lung cancer treatment

2021 ◽  
Author(s):  
Ashley E Glode ◽  
Megan B May
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Novel Therapies ◽  
Small Cell Lung

Abstract Purpose This article explores the efficacy, toxicity, place in therapy, and considerations for use of recently approved immune checkpoint inhibitors (ICIs) in the treatment of non–small cell lung cancer (NSCLC). Summary Lung cancer is the leading cause of cancer mortality in the United States and is responsible for more cancer-related deaths than breast, prostate, and colorectal cancer combined. The landscape for lung cancer treatment is evolving with the approval of new and exciting novel therapies. Within the last decade numerous ICIs have been approved for use in the management of the most common subtype of lung cancer, NSCLC. The ICI agents currently approved by the Food and Drug Administration (FDA) for use in NSCLC include ipilimumab, pembrolizumab, nivolumab, durvalumab, and atezolizumab. These agents are approved for specific indications; therefore, they are not interchangeable. This review focuses on the landmark trials that led to each FDA-approved indication, as well as common toxicities seen with use of these agents. It also discusses the use of ICIs in special populations and unique considerations prior to initiation of treatment with these novel therapies in a patient with NSCLC. Conclusion ICIs can provide a breakthrough treatment option for the management of NSCLC and are rapidly being adopted into clinical practice. It is important to be familiar with appropriate selection of an ICI therapy option for each patient based on approved indication, unique considerations, and anticipated toxicities.

scholarly journals Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4931 ◽  
Author(s):  
Andrea Bianco ◽  
Fabio Perrotta ◽  
Giusi Barra ◽  
Umberto Malapelle ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
T Cell Subsets ◽  
Durable Response ◽  
Lung Cancer Treatment ◽  
The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

scholarly journals Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000144 ◽  
Author(s):  
Sarah Abou Alaiwi ◽  
Wanling Xie ◽  
Amin H Nassar ◽  
Shaan Dudani ◽  
Dylan Martini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Median Time ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Safety And Efficacy ◽  
Clinically Significant

BackgroundImmune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.MethodsThis multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1 week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.ResultsOf 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2–31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3–13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95% CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.ConclusionsDespite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.

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