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 Progress in Adenoviral Capsid-Display Vaccines

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 81 ◽  
Author(s):  
Marija Vujadinovic ◽  
Jort Vellinga
Keyword(s):  
Immune Responses ◽  
Adenoviral Vector ◽  
Vaccine Development ◽  
Adenoviral Vectors ◽  
Manufacturing Costs ◽  
Genetic Vaccine ◽  
Immunogenic Peptides ◽  
T Cell Immune Responses ◽  
Protein Ix ◽  
Capsid Display

Adenoviral vectored vaccines against infectious diseases are currently in clinical trials due to their capacity to induce potent antigen-specific B- and T-cell immune responses. Heterologous prime-boost vaccination with adenoviral vector and, for example, adjuvanted protein-based vaccines can further enhance antigen-specific immune responses. Although leading to potent immune responses, these heterologous prime-boost regimens may be complex and impact manufacturing costs limiting efficient implementation. Typically, adenoviral vectors are engineered to genetically encode a transgene in the E1 region and utilize the host cell machinery to express the encoded antigen and thereby induce immune responses. Similarly, adenoviral vectors can be engineered to display foreign immunogenic peptides on the capsid-surface by insertion of antigens in capsid proteins hexon, fiber and protein IX. The ability to use adenoviral vectors as antigen-display particles, with or without using the genetic vaccine function, greatly increases the versatility of the adenoviral vector for vaccine development. This review describes the application of adenoviral capsid antigen-display vaccine vectors by focusing on their distinct advantages and possible limitations in vaccine development.

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 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.

scholarly journals A Polypeptide of Tumor-Associated Antigen L6 with Intrinsic Adjuvant Activity Enhances Antitumor Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 620
Author(s):  
Yuh-Pyng Sher ◽  
Kit Man Chai ◽  
Wen-Ching Chen ◽  
Kuan-Yin Shen ◽  
I-Hua Chen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Antitumor Immunity ◽  
Cell Epitope ◽  
Specific Treatment ◽  
T Helper Cell ◽  
Helper Cell ◽  
Peptide Vaccines ◽  
T Helper ◽  
Tumor Associated Antigen

Peptide vaccines are safe, and aim to elicit and expand tumor-specific immunity so as to eradicate tumors. However, achieving strong and long-lasting anti-tumor immunity with peptide vaccines for the antigen-specific treatment of cancer is challenging, in part because their efficacy depends on strong adjuvants or immunomodulators. We approached this problem by conjugating an epitope-based cancer vaccine with a lipidated sequence (an immunomodulator) to elicit a strong immune response. Lipidated and non-lipidated polyepitope proteins were generated that contained the universal T helper cell epitope (pan-DR), B cell epitopes, and the extended loop sequence of extracellular domain 2 of tumor-associated antigen L6 (TAL6). We show that the lipidated polyepitope cancer vaccine can activate bone marrow-derived dendritic cells, and trigger effective antigen-specific antibody and T helper cell responses, more effectively than the non-lipidated vaccine. Moreover, potent T cell immune responses were elicited in mice inoculated with the lipidated polyepitope cancer vaccine, providing protective antitumor immunity in mice bearing TAL6 tumors. Our study demonstrates that a lipidated polyepitope cancer vaccine could be employed to generate potent anti-tumor immune responses, including humoral and cellular immunity, which could be beneficial in the treatment of TAL6+ cancer.

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