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 mm) 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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712481 | PMC |
http://dx.doi.org/10.3390/vaccines8040655 | DOI Listing |
J Immunother Cancer
September 2023
Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Background: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.
View Article and Find Full Text PDFVaccines (Basel)
November 2020
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
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 mm) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy.
Vaccines (Basel)
June 2020
Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles, Healthcare System, 11301, Wilshire Blvd, Los Angeles, CA 90073, USA.
: Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the activation of immune responses against cancer. Therapeutic vaccination, which induces specific immune responses against tumor antigens (Ags), is an attractive option. : Utilizing a K-RasG12Dp53null murine lung cancer model we determined tumor burden, tumor-infiltrating T cell (TIL) cytolysis, immunohistochemistry, flow cytometry, and CD4 and CD8 depletion to evaluate the efficacy of PD-1 blockade combined with CCL21-DC tumor lysate vaccine.
View Article and Find Full Text PDFClin Cancer Res
August 2017
Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California.
A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following vaccination (ClinicalTrials.gov: NCT01574222).
View Article and Find Full Text PDFOtolaryngol Head Neck Surg
September 2014
Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, California, USA UCLA Head and Neck Cancer Program, University of California, Los Angeles, Los Angeles, California, USA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California, USA
Objective: This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC).
Study Design: In vivo study.
Setting: Academic research laboratory.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!