Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine

Chen, Tingting; Liu, Kan; Xu, Jiangyao; Zhan, Tianying; Liu, Maixian; Li, Li; Yang, Zhiwen; Yuan, Shuping; Zou, Wenyi; Lin, Guimiao; Carson, Dennis A.; Wu, Christina; Wang, Xiaomei

doi:10.20892/j.issn.2095-3941.2019.0224

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…We believe that the Th cells’ activation was potentiated by the presence of KLH, which likely led to the enhanced production of IFN-γ and IL-2. Our findings are in line with those studies that used KLH as an adjuvant in the development of peptide-based vaccines [ 38 ]. The Th cell proliferation and CTL response were stimulated in an antigen-specific manner in which the sera from immunized mice were found to be selective in inducing cytotoxic effects only against TUBO cells but not towards normal cells (HEK293).…”

Section: Discussionsupporting

confidence: 92%

HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model

Nordin

Norpi

et al. 2021

Cancers

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Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor T-cell responses of the HER2/neu oncogene, which is abnormally expressed in breast cancer cells. However, the role of the B-cell humoral response is often underappreciated in the cancer vaccine design. We have advanced this idea by elucidating the role of B-cells in cancer vaccination by designing a chimeric antigenic peptide possessing both cytotoxic T lymphocytes (GP2) and B-cell (P4) peptide epitopes derived from HER2/neu. The chimeric peptide (GP2–P4) was further conjugated to a carrier protein (KLH), forming a KLH–GP2–P4 conjugate. The immunogenicity of KLH–GP2–P4 was compared with KLH–GP2 (lacking the B-cell epitope) in BALB/c mice. Mice immunized with KLH–GP2–P4 elicited more potent antigen-specific neutralizing antibodies against syngeneic TUBO cells (cancer cell line overexpressing HER2/neu) that was governed by a balanced Th1/Th2 polarization in comparison to KLH–GP2. Subsequently, these immune responses led to greater inhibition of tumor growth and longer survival in TUBO tumor-bearing mice in both prophylactic and therapeutic challenge experiments. Overall, our data demonstrated that the B-cell epitope has a profound effect in orchestrating an efficacious antitumor immunity. Thus, a multi-epitope peptide vaccine encompassing cytotoxic T-lymphocytes, T-helper and B-cell epitopes represents a promising strategy in developing cancer vaccines with a preventive and therapeutic modality for the effective management of breast cancer.

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Section: Discussionsupporting

confidence: 92%

HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model

Nordin

Norpi

et al. 2021

Cancers

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“… 162 In a similar study published by Chen et al, a vaccine was designed to target stem-cell-like cancer cells by chemically conjugating an OCT4-specific peptide with carrier protein keyhole limpet hemocyanin (KLH) and a TLR9 agonist. 163 Vaccination of F9 teratocarcinoma-bearing mice led to slower tumor growth and longer survival, compared to mice treated with TLR9 agonist or OCT4-KLH alone. Analysis of the tumor showed increased infiltration of CD8+ T cells, and secretion of pro-inflammatory cytokines such as IL-2, IL-6, and IL-12.…”

Section: Preclinical Approaches Using Tlr Agonists As Cancer Vaccine ...mentioning

confidence: 99%

Toll-like receptor agonists as cancer vaccine adjuvants

Jeon,

Hill,

McNeel

2023

Human Vaccines & Immunotherapeutics

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Cancer immunotherapy has emerged as a promising strategy to treat cancer patients. Among the wide range of immunological approaches, cancer vaccines have been investigated to activate and expand tumor-reactive T cells. However, most cancer vaccines have not shown significant clinical benefit as monotherapies. This is likely due to the antigen targets of vaccines, “self” proteins to which there is tolerance, as well as to the immunosuppressive tumor microenvironment. To help circumvent immune tolerance and generate effective immune responses, adjuvants for cancer vaccines are necessary. One representative adjuvant family is Toll-Like receptor (TLR) agonists, synthetic molecules that stimulate TLRs. TLRs are the largest family of pattern recognition receptors (PRRs) that serve as the sensors of pathogens or cellular damage. They recognize conserved foreign molecules from pathogens or internal molecules from cellular damage and propel innate immune responses. When used with vaccines, activation of TLRs signals an innate damage response that can facilitate the development of a strong adaptive immune response against the target antigen. The ability of TLR agonists to modulate innate immune responses has positioned them to serve as adjuvants for vaccines targeting infectious diseases and cancers. This review provides a summary of various TLRs, including their expression patterns, their functions in the immune system, as well as their ligands and synthetic molecules developed as TLR agonists. In addition, it presents a comprehensive overview of recent strategies employing different TLR agonists as adjuvants in cancer vaccine development, both in pre-clinical models and ongoing clinical trials.

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“…Octamer-binding transcription factor 4 (OCT4) is among the key transcription factors involved in the regulation of self-renewal and maintenance of pluripotent embryonic stem cells. 39 , 40 Some studies indicate OCT4 is expressed in CSCs, especially in the early stages of tumorigenesis. 41 Thus, it is one of the areas scientists have been targeting in seeking a cure for cancers.…”

Section: Potential Alternative Treatment Options For Head and Neck Sq...mentioning

confidence: 99%

“…Chen and colleagues 40 assessed the effectiveness of the OCT4 vaccine as an anti-tumor using BALB/c mice vaccinated with the combination vaccine (OCT4-3 + TLR9). Their findings revealed that in the OCT4-3 + TLR9 vaccine group, the tumors grew slowly and shrunk significantly.…”

Section: Potential Alternative Treatment Options For Head and Neck Sq...mentioning

confidence: 99%

Potential Alternative Therapeutic Modalities for Management Head and Neck Squamous Cell Carcinoma: A Review

Afshari,

Sohal

2023

Cancer Control

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Head and neck squamous cell carcinoma (HNSCC) includes malignancies of the lip and oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx. It is among the most common malignancy worldwide, affecting nearly 1 million people annually. The traditional treatment options for HNSCC include surgery, radiotherapy, and conventional chemotherapy. However, these treatment options have their specific sequelae, which produce high rates of recurrence and severe treatment-related disabilities. Recent technological advancements have led to tremendous progress in understanding tumor biology, and hence the emergence of several alternative therapeutic modalities for managing cancers (including HNSCC). These treatment options are stem cell targeted therapy, gene therapy, and immunotherapy. Therefore, this review article aims to provide an overview of these alternative treatments of HNSCC.

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Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine

Cited by 6 publications

References 28 publications

HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model

HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model

Toll-like receptor agonists as cancer vaccine adjuvants

Potential Alternative Therapeutic Modalities for Management Head and Neck Squamous Cell Carcinoma: A Review

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