Cancers, Vol. 12, Pages 810: Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells

Cancers, Vol. 12, Pages 810: Liposomal TLR9 Agonist Combined with TLR2 Agonist-Fused Antigen Can Modulate Tumor Microenvironment through Dendritic Cells Cancers doi: 10.3390/cancers12040810 Authors: Kuan-Yin Shen Hsin-Yu Liu Wan-Lun Yan Chiao-Chieh Wu Ming-Hui Lee Chih-Hsing Leng Shih-Jen Liu Dendritic cells (DCs) are antigen-presenting cells involved in T cell activation and differentiation to regulate immune responses. Lipoimmunogens can be developed as pharmaceutical lipoproteins for cancer immunotherapy to target DCs via toll-like receptor 2 (TLR2) signaling. Previously, we constructed a lipoimmunogen, a lipidated human papillomavirus (HPV) E7 inactive mutant (rlipoE7m), to inhibit the growth of HPV16 E7-expressing tumor cells in a murine model. Moreover, this antitumor effect could be enhanced by a combinatory treatment with CpG oligodeoxynucleotides (ODN). To improve safety, we developed a rlipoE7m plus DOTAP liposome-encapsulated native phosphodiester CpG (POCpG/DOTAP) treatment to target DCs to enhance antitumor immunity. We optimized the formulation of rlipoE7m and POCpG/DOTAP liposomes to promote conventional DC and plasmacytoid DC maturation in vitro and in vivo. Combination of rlipoE7m plus POCpG/DOTAP could activate conventional DCs and plasmacytoid DCs to augment IL-12 production to promote antitumor responses by intravenous injection. In addition, the combination of rlipoE7m plus POCpG/DOTAP could elicit robust cytotoxic T lymphocytes (CTLs)...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Human papillomavirus (HPV) is the most common sexually transmitted virus. The high-risk HPV types (i.e., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) are considered to be the main etiological agents of genital tract cancers, such as cervical, vulvar, vaginal, penile, and anal cancers, and of a subset of head and neck cancers. Three prophylactic HPV vaccines are available that are bivalent (vs. HPV16, 18), tetravalent (vs. HPV6, 11, 16, 18), and non-avalent (vs. HPV6, 11, 16, 18, 31, 33,45, 52, 58). All of these vaccines are based on recombinant DNA technology, and they are prepared from the purified L1 protein that s...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Human papillomavirus (HPV)-induced cervical cancer is a major health issue among women from the poorly/under-developed sectors of the world. It accounts for a high-mortality rate because of its late diagnosis and poor prognosis. Initial establishment and subsequent progression of this form of cancer are completely dependent on two major oncogenes E6 and E7, which are expressed constitutively leading to tumorigenesis. Thus, manipulation of these genes represents the most successful form of cervical cancer therapy. In the present article, information on structural, functional, and clinical dimensions of E6 and E7 activity ha...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract The accumulating successes of immune-based treatments for solid tumors have prompted an explosion of cancer clinical trials testing strategies to elicit tumor-specific immune effector responses, either alone, in combination with immune checkpoint blockade, or with conventional cancer treatment modalities. However, across the board, clinical responses have been achieved in only a limited subset of cancer patients, underscoring a critical need to identify mechanisms and biomarkers of response, as well as mechanisms of resistance to therapy. Cancers caused by human papillomavirus (HPV) are driven by two vira...
Source: Gynecologic Oncology - Category: Cancer & Oncology Authors: Tags: Gynecol Oncol Source Type: research
Persistent infection with human papillomavirus (HPV) initiates ~5% of all human cancers, and particularly cervical and oropharyngeal cancers. HPV vaccines prevent HPV infection, but do not eliminate existing HPV infections. Papillomaviruses induce hyperproliferation of epithelial cells. In this review we discuss how hyperproliferation renders epithelial cells less sensitive to immune attack, and impacts upon the efficiency of the local immune system. These observations have significance for the design of therapeutic HPV cancer immunotherapies.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractHuman papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are elimina...
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research
AbstractHigh-risk human papillomavirus (HPV) are responsible for genital and oral cancers associated with the expression of the E6/E7 HPV oncogenes. Therapeutic vaccines targeting those oncogenes can only partially control tumor progression, highlighting the necessity to investigate different treatment strategies. Using the genital orthotopic HPV16 TC-1 model, herein we sequentially investigated in progressively more stringent settings the effects of systemic administration of carboplatin/paclitaxel (C  + P) chemotherapy combined with HPV16-E7 synthetic long peptide (E7LP) vaccination, followed by intravagina...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractCancer immunotherapy has greatly advanced in recent years. Most immunotherapeutic strategies are based on the use of immune checkpoint blockade to unleash antitumor immune responses or on the induction or adoptive transfer of immune effector cells. We aim to develop therapeutic vaccines based on recombinant Semliki Forest virus vectors to induce tumor-specific effector immune cells. In this review, we describe our ongoing work on SFV-based vaccines targeted against human papillomavirus- and hepatitis C virus-related infections and malignancies, focusing on design, delivery, combination strategies, preclinical effic...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Human papillomavirus (HPV) has been associated with the cause of several cancer types, including cervical, anal, and head and neck cancers. There has been great success in preventing HPV infections with the development of prophylactic HPV vaccines, Gardasil and Cervarix. However, these vaccines have only been shown to prevent HPV infection and not treat those already infected with HPV. These vaccines elicit antibody responses to late HPV genes, and thus would not be effective in treating established tumors. To date, no therapeutic HPV vaccine has been approved by the FDA, and there is an unmet need for therapeutic vaccines...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
(University of Pennsylvania School of Medicine) A therapeutic vaccine can boost antibodies and T cells, helping them infiltrate tumors and fight off human papillomavirus (HPV)-related head and neck cancer. Researchers from the Abramson Cancer Center of the University of Pennsylvania tested the immunotherapy approach in two groups of patients with advanced head and neck squamous cell carcinoma (HNSCCa) and found 86 percent showed elevated T cell activity.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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