scholarly journals CCL21-DC tumor antigen vaccine augments anti-PD-1 therapy in lung cancer

2021 ◽  
Vol 8 (4) ◽  
pp. 269-275
Author(s):  
Sherven Sharma ◽  
◽  
Pournima Kadam ◽  
Ram P Singh ◽  
Michael Davoodi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Tumor Antigen ◽  
Immune Checkpoint ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Treatment Modalities ◽  
Therapeutic Cancer Vaccines

<abstract> <p>Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the induction and activation of an immune response against cancer. Therapeutic vaccination, which can induce a specific immune response against tumor antigens, is an important approach to consider. Although this approach has shown low clinical efficacy when combined with other treatment modalities, therapeutic cancer vaccines will have a better outcome when combined with immune checkpoint blockade therapy with potential for cancer free survival. In this review, we will discuss the results of our two recent publications in preclinical lung cancer models. Our studies reveal that anti-PD-1 administered in combination with CCL21-DC tumor antigen therapeutic vaccines eradicate lung cancer. The results of these studies highlight the importance of combination therapy of immune checkpoint blockade and therapeutic cancer vaccines for lung cancer patients.</p> </abstract>

New Strategies for Therapeutic Cancer Vaccines

2019 ◽  
Vol 19 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Hanjiao Qin ◽  
Jiyao Sheng ◽  
Dan Zhang ◽  
Xuewen Zhang ◽  
Linlin Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Cancer Stem Cell ◽  
Continuous Improvement ◽  
Immune Checkpoint ◽  
Cancer Vaccines ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Therapeutic Effects ◽  
Therapeutic Cancer Vaccines

Background: Patients with low response rates to cancer vaccines, short duration of anti-tumor response after vaccination, and relatively weak curative effects are problems that have not been resolved effectively during the development and application of cancer vaccines. With the continuous improvement of knowledge and awareness regarding the immune system and cancer cells, many researches have helped to explain the reasons for poor vaccine efficacy. Input from researchers accompanied by some newly emerged strategies could bring hope to improve the therapeutic effects of vaccines. Methods: Data were collected from Web of Science, Medline, Pubmed, through searching of these keywords: “cancer vaccine”, “cancer stem cell”, “targeted agent”, “immune checkpoint blockade” and “neoantigen”. Results: It may be more effective in immunotherapy of human cancers, including cancer stem cell vaccines, combination vaccines with targeted agents or immune checkpoint blockade, and neoantigen-based vaccines. Conclusion: Personalized vaccines will become the mainstream solution of cancer treatment program with the continuous improvement of human understanding of the immune system and the progress of related experiments.

scholarly journals Immune Checkpoint Blockade Enhances Immune Activity of Therapeutic Lung Cancer Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 655
Author(s):  
Pournima Kadam ◽  
Ram P. Singh ◽  
Michael Davoodi ◽  
Jay M. Lee ◽  
Maie St. John ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Immune Checkpoint ◽  
Neutralizing Antibodies ◽  
Combined Therapy ◽  
Immune Checkpoint Blockade ◽  
Tumor Burden ◽  
Checkpoint Blockade ◽  
Lung Cancer Patients ◽  
Therapeutic Cancer Vaccines

Background: Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines. Methods: Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine. Results: Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm3) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies. Conclusion: PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.

scholarly journals Clinical management of immune-related adverse events following immunotherapy treatment in patients with non-small cell lung cancer

2021 ◽  
pp. jim-2021-001806
Author(s):  
Hannah Elizabeth Green ◽  
Jorge Nieva
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Immune Checkpoint ◽  
Clinical Management ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Checkpoint Blockade ◽  
Small Cell Lung ◽  
Autoimmune Conditions

The advent of checkpoint blockade-based immunotherapy is rapidly changing the management of lung cancer. Whereas past anticancer drugs’ primary toxicity was hematologic, the newer agents have primarily autoimmune toxicity. Thus, it is no longer enough for oncology practitioners to be skilled only in hematology. They must also understand management of autoimmune conditions, leveraging the skills of the rheumatologist, endocrinologist and gastroenterologist in the process. Herein we describe the mechanism of action and toxicities associated with immune checkpoint blockade in patients with lung cancer and provide a framework for management of adverse events.

scholarly journals Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma

2015 ◽  
Vol 21 (20) ◽  
pp. 4607-4618 ◽  
Author(s):  
Güllü Görgün ◽  
Mehmet K. Samur ◽  
Kristen B. Cowens ◽  
Steven Paula ◽  
Giada Bianchi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

scholarly journals Combination of epigenetic regulation with gene therapy-mediated immune checkpoint blockade induces anti-tumour effects and immune response in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huapan Fang ◽  
Zhaopei Guo ◽  
Jie Chen ◽  
Lin Lin ◽  
Yingying Hu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Epigenetic Regulation ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Immune Memory ◽  
Escape Mechanism ◽  
Immune Escape Mechanism

AbstractImmunotherapy has become a powerful cancer treatment, but only a small fraction of patients have achieved durable benefits due to the immune escape mechanism. In this study, epigenetic regulation is combined with gene therapy-mediated immune checkpoint blockade to relieve this immune escape mechanism. PPD (i.e., mPEG-b-PLG/PEI-RT3/DNA) is developed to mediate plasmid-encoding shPD-L1 delivery by introducing multiple interactions (i.e., electrostatic, hydrogen bonding, and hydrophobic interactions) and polyproline II (PPII)-helix conformation, which downregulates PD-L1 expression on tumour cells to relieve the immunosuppression of T cells. Zebularine (abbreviated as Zeb), a DNA methyltransferase inhibitor (DNMTi), is used for the epigenetic regulation of the tumour immune microenvironment, thus inducing DC maturation and MHC I molecule expression to enhance antigen presentation. PPD plus Zeb combination therapy initiates a systemic anti-tumour immune response and effectively prevents tumour relapse and metastasis by generating durable immune memory. This strategy provides a scheme for tumour treatment and the inhibition of relapse and metastasis.

scholarly journals Trousseau's syndrome triggered by an immune checkpoint blockade in a non-small cell lung cancer patient

2018 ◽  
Vol 48 (10) ◽  
pp. 1764-1767 ◽  
Author(s):  
Yuko Horio ◽  
Koutaro Takamatsu ◽  
Daisuke Tamanoi ◽  
Ryo Sato ◽  
Koichi Saruwatari ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patient ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Lung Cancer Patient ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Checkpoint Blockade ◽  
Small Cell Lung

scholarly journals O4 Mechanisms of lung cancer hyper-progression promoted by PD-1 immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A5.1-A5
Author(s):  
A Martinez-Usatorre ◽  
E Kadioglu ◽  
C Cianciaruso ◽  
B Torchia ◽  
J Faget ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Genetically Engineered ◽  
Checkpoint Blockade ◽  
Therapeutic Benefits ◽  
Angiopoietin 2

BackgroundImmune checkpoint blockade (ICB) with antibodies against PD-1 or PD-L1 may provide therapeutic benefits in patients with non-small cell lung cancer (NSCLC). However, most tumours are resistant and cases of disease hyper-progression have also been reported.Materials and MethodsGenetically engineered mouse models of KrasG12Dp53null NSCLC were treated with cisplatin along with antibodies against angiopoietin-2/VEGFA, PD-1 and CSF1R. Tumour growth was monitored by micro-computed tomography and the tumour vasculature and immune cell infiltrates were assessed by immunofluorescence staining and flow cytometry.ResultsCombined angiopoietin-2/VEGFA blockade by a bispecific antibody (A2V) modulated the vasculature and abated immunosuppressive macrophages while increasing CD8+effector T cells in the tumours, achieving disease stabilization comparable or superior to cisplatin-based chemotherapy. However, these immunological responses were unexpectedly limited by the addition of a PD-1 antibody, which paradoxically enhanced progression of a fraction of the tumours through a mechanism involving regulatory T cells and macrophages. Elimination of tumour-associated macrophages with a CSF1R-blocking antibody induced NSCLC regression in combination with PD-1 blockade and cisplatin.ConclusionsThe immune cell composition of the tumour determines the outcome of PD-1 blockade. In NSCLC, high infiltration of regulatory T cells and immunosuppressive macrophages may account for tumour hyper-progression upon ICB.Disclosure InformationA. Martinez-Usatorre: None. E. Kadioglu: None. C. Cianciaruso: None. B. Torchia: None. J. Faget: None. E. Meylan: None. M. Schmittnaegel: None. I. Keklikoglou: None. M. De Palma: None.

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