scholarly journals CpG Oligodeoxynucleotide Developed to Activate Primate Immune Responses Promotes Antitumoral Effects in Combination with a Neoantigen-Based mRNA Cancer Vaccine

2021 ◽  
Vol Volume 15 ◽  
pp. 3953-3963
Author(s):  
Qin Li ◽  
Jie Ren ◽  
Wei Liu ◽  
Guoqin Jiang ◽  
Rongkuan Hu
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cpg Oligodeoxynucleotide

scholarly journals CpG Oligodeoxynucleotide Developed For Activating Primate Immune Responses Promotes Anti-Tumoral Effect Combine With Neo-Antigen Based mRNA Cancer Vaccine

2021 ◽  
Author(s):  
Rongkuan Hu ◽  
Qin Li ◽  
Jie Ren ◽  
Wei Liu ◽  
Guoqin Jiang
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Cytokine Production ◽  
Toll Like Receptor ◽  
Human Pbmc ◽  
Cpg Oligodeoxynucleotides ◽  
Adaptive Immune ◽  
Cpg Oligodeoxynucleotide

Abstract Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.

Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice

2005 ◽  
Vol 108 (2-3) ◽  
pp. 294-305 ◽  
Author(s):  
Joe Inoue ◽  
Satoshi Yotsumoto ◽  
Takatoshi Sakamoto ◽  
Seishi Tsuchiya ◽  
Yukihiko Aramaki
Keyword(s):  
Immune Responses ◽  
Cpg Oligodeoxynucleotide

Rhamnose modified bovine serum albumin as a carrier protein promotes the immune response against sTn antigen

2020 ◽  
Vol 56 (90) ◽  
pp. 13959-13962
Author(s):  
Han Lin ◽  
Haofei Hong ◽  
Jinfeng Wang ◽  
Chen Li ◽  
Zhifang Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Serum Albumin ◽  
Cancer Vaccine ◽  
Bovine Serum ◽  
Vaccine Development ◽  
Carrier Protein ◽  
Antigen Uptake ◽  
Specific Antibodies

Rhamnose and sTn antigen were co-conjugated to bovine serum albumin (BSA) for cancer vaccine development. The immune responses against sTn have been significantly augmented with the involvement of Rha-specific antibodies to enhance antigen uptake.

Humoral Immune Response to a Therapeutic Polyvalent Cancer Vaccine After Complete Resection of Thick Primary Melanoma and Sentinel Lymphadenectomy

2003 ◽  
Vol 21 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Mathew H. Chung ◽  
Rishab K. Gupta ◽  
Eddy Hsueh ◽  
Richard Essner ◽  
Wei Ye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cutaneous Melanoma ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Vaccine Therapy ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Primary Cutaneous Melanoma ◽  
Sentinel Lymphadenectomy

Purpose: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick (≥ 4 mm) primary cutaneous melanoma. Patients and Methods: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course. Results: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P = .184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P = .0006 and .006, respectively) but not with maximal IgG response (P = .73 and .95, respectively). Neither response predicted survival in the observation group. Conclusion: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.

scholarly journals Changes in Immune Responses to Mite Antigen Sensitized through Barrier-Disrupted Skin with CpG-Oligodeoxynucleotide in Mice

2006 ◽  
Vol 29 (2) ◽  
pp. 385-387 ◽  
Author(s):  
Joe Inoue ◽  
Satoshi Yotsumoto ◽  
Takatoshi Sakamoto ◽  
Seishi Tsuchiya ◽  
Yukihiko Aramaki
Keyword(s):  
Immune Responses ◽  
Cpg Oligodeoxynucleotide

scholarly journals Cancer vaccine based on a combination of an infection-enhanced adenoviral vector and pro-inflammatory allogeneic DCs leads to sustained antigen-specific immune responses in three melanoma models

2017 ◽  
Vol 7 (3) ◽  
pp. e1397250 ◽  
Author(s):  
Grammatiki Fotaki ◽  
Chuan Jin ◽  
Iliana Kyriaki Kerzeli ◽  
Mohanraj Ramachandran ◽  
Minttu-Maria Martikainen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Adenoviral Vector

scholarly journals Microarray Analysis for a Comprehensive Immunological-Status Evaluation during Cancer Vaccine Immune Monitoring

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Vladia Monsurrò ◽  
Francesco M. Marincola
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Single Cell Analysis ◽  
Immune Therapy ◽  
Immune Monitoring ◽  
Host Responses ◽  
Cell Analysis ◽  
Biological Mechanisms ◽  
High Throughput Gene Expression ◽  
Reductionist Approach

Anticancer immune responses can be enhanced by immune intervention that promotes complex biological mechanisms involving several cellular populations. The classical immune monitoring for biological-based cancer clinical trials is often based on single-cell analysis. However, the overall effect could be lost by such a reductionist approach explaining the lack of correlation among clinical and immunological endpoints often reported. Microarray technology could give the possibility of studying in a multiparametric setting the immune therapy effects. The application of microarray is leading to an improved understanding of the immune responses to tumor immunotherapy. In fact, analysis of cancer vaccine-induced host responses using microarrays is proposed as valuable alternative to the standard cell-based methods. This paper shows successful examples of how high-throughput gene expression profiling contributed to the understanding of anticancer immune responses during biological therapy, introducing as well the integrative platforms that allow the network analysis in molecular biology studies.

scholarly journals Mathematical model of a personalized neoantigen cancer vaccine and the human immune system

2021 ◽  
Vol 17 (9) ◽  
pp. e1009318
Author(s):  
Marisabel Rodriguez Messan ◽  
Osman N. Yogurtcu ◽  
Joseph R. McGill ◽  
Ujwani Nukala ◽  
Zuben E. Sauna ◽  
...  
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Tumor Size ◽  
Cancer Vaccines ◽  
Patient Specific ◽  
Human Immune System ◽  
Human Immune

Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient’s immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient’s major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.

scholarly journals PD-1 Immune Checkpoint Blockade Promotes Therapeutic Cancer Vaccine to Eradicate Lung Cancer

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 317 ◽  
Author(s):  
Pournima Kadam ◽  
Sherven Sharma
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Vaccine ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Tumor Burden ◽  
Tumor Lysate ◽  
Therapeutic Cancer Vaccine ◽  
Tumor Eradication

(1) Background: 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. (2) Methods: 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. (3) Results: Anti-PD-1 plus CCL21-DC tumor lysate vaccine administered to mice bearing established tumors (150 mm3) increased expression of perforin and granzyme B in the tumor microenvironment (TME), increased tumor-infiltrating T cell (TIL) activity, and caused 80% tumor eradication. Mice with treatment-induced tumor eradication developed immunological memory, enabling tumor rejection upon challenge and cancer-recurrence-free survival. The depletion of CD4 or CD8 abrogated the antitumor activity of combined therapy. PD-1 blockade or CCL21-DC tumor lysate vaccine monotherapy reduced tumor burden without tumor eradication. (4) Conclusion: Immune checkpoint blockade promotes the activity of the therapeutic cancer vaccine. PD-1 blockade plus CCL21-DC tumor lysate vaccine therapy could benefit lung cancer patients.

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