Vaccines and immune checkpoint inhibitors: a promising combination strategy in gastrointestinal cancers

Immunotherapy ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 561-564
Author(s):  
Babar Bashir ◽  
John C Flickinger ◽  
Adam E Snook

Tweetable abstract US FDA-approved immune checkpoint inhibitors have limited efficacy for gastrointestinal cancers such as #colorectalcancer and #pancreaticcancer. Could combinations with experimental cancer ‘vaccines’ be the key?

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2495
Author(s):  
Kazuhiko Matsuo ◽  
Osamu Yoshie ◽  
Kosuke Kitahata ◽  
Momo Kamei ◽  
Yuta Hara ◽  
...  

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.


2021 ◽  
Vol 64 (5) ◽  
pp. 342-348
Author(s):  
Jin Won Kim

Immuno-oncological treatment approaches, particularly with the use of immune checkpoint inhibitors such as antiprogrammed death 1 (PD-1)/programmed death ligand 1 antibody or anti-cytotoxic T-lymphocyte associated protein 4 antibody, have become the standard treatment for gastrointestinal cancers. However, gastrointestinal cancers show an overall modest tumor response to immune checkpoint inhibitors. Nevertheless, subgroups such as tumors that are DNA mismatch repair-deficient or have high microsatellite instability particularly benefit from immune checkpoint inhibitors. Even in the first-line setting for colorectal cancer, the clinical efficacy of pembrolizumab, an anti–PD-1 antibody, was superior to that of chemotherapy. Recently, a combination of atezolizumab, an anti-programmed death ligand 1 antibody, and bevacizumab was approved as the first-line treatment for hepatocellular carcinoma, and was reported as superior to sorafenib. Nivolumab, an anti–PD-1 antibody that is added to chemotherapy as the first-line treatment for gastric cancer, resulted in longer survival compared with chemotherapy alone. Further studies are ongoing to investigate additional immune checkpoint inhibitors for other gastrointestinal cancers. This review aims to provide an overview of the results of clinical trials for immune checkpoint inhibitors in gastrointestinal cancers, including colorectal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer.


Immunotherapy ◽  
2021 ◽  
Author(s):  
Nikolaos Charalampakis ◽  
Georgios Papageorgiou ◽  
Sergios Tsakatikas ◽  
Rodanthi Fioretzaki ◽  
Christo Kole ◽  
...  

Cholangiocarcinoma (CCA) is a rare malignancy with generally dismal prognosis. Immunotherapy has revolutionized the management of cancer patients during the last decade, offering durable responses with an acceptable safety profile, but there are still no significant advances regarding CCA. Novel immunotherapeutic methods, such as cancer vaccines, oncolytic viruses, adoptive cell therapy and combinations of immune checkpoint inhibitors with other agents are currently under investigation and may improve prognosis. Efforts to find robust biomarkers for response are also ongoing. In this review, we discuss the rationale for the use of immunotherapy in CCA and available clinical data. Ongoing trials will also be presented, as well as key findings from each study.


2021 ◽  
Vol 11 ◽  
Author(s):  
Juan-Yan Liao ◽  
Shuang Zhang

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.


2021 ◽  
Vol 10 ◽  
Author(s):  
Clelia Donisi ◽  
Marco Puzzoni ◽  
Pina Ziranu ◽  
Eleonora Lai ◽  
Stefano Mariani ◽  
...  

Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.


Immunotherapy ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 587-603
Author(s):  
Mobina Jalalvand ◽  
Farzaneh Darbeheshti ◽  
Nima Rezaei

Cancer initiation and progression are associated with immune system responses. Tumor cells use various tricks to scape of immune system, such as activating immune checkpoint pathways that induce immunosuppressive functions. Among the different immune checkpoint receptors, CTLA-4 and PD-1/PD-L1 are prominent therapeutic targets in different cancers. Although the US FDA has approved some immune checkpoint inhibitors for several cancers, concerning breast cancer still different clinical trials are looking for optimizing efficacy and decreasing immune-related adverse events. This review will discuss the existing body of knowledge with regard to cross-talk between immune system and tumor cells and then explore immune checkpoint-related signaling pathways in the context of breast tumors. Finally, we highlight the application of different immune checkpoint blockers in breast cancer patients.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 586 ◽  
Author(s):  
Cyrillo G. Brahm ◽  
Myra E. van Linde ◽  
Roelien H. Enting ◽  
Maaike Schuur ◽  
René H.J. Otten ◽  
...  

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.


2020 ◽  
Vol 11 ◽  
Author(s):  
Joshua Tobias ◽  
Claire Battin ◽  
Annika De Sousa Linhares ◽  
Michael Lebens ◽  
Karin Baier ◽  
...  

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