Tumor Antigens and Immune Regulation in Cancer Immunotherapy

Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol-chitosan-coated gold nanoparticles (GC-AuNPs), which highlighted lymph nodes in ultrasound-guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC-AuNPs (OVA-GC-AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA-GC-AuNPs were used for cellular uptake. After the lingual injection of GC-AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three-dimensional analysis of lymph nodes revealed that the accumulation of GC-AuNPs in the lymph node increased as the post-injection time passed. Histological analysis showed GC-AuNPs or OVA-GC-AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC-AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC-AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.

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The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy

Cancers ◽

10.3390/cancers13143596 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3596

Author(s):

Reza Bayat Mokhtari ◽

Manpreet Sambi ◽

Bessi Qorri ◽

Narges Baluch ◽

Neda Ashayeri ◽

...

Keyword(s):

Immune System ◽

Cancer Immunotherapy ◽

Tumor Cells ◽

Tumor Antigens ◽

Response Rates ◽

Viral Proteins ◽

Tumor Rejection ◽

Therapeutic Approaches ◽

Patient Response ◽

Specific Antigens

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.

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Cancer Immunotherapy: A Review

The Indonesian Biomedical Journal ◽

10.18585/inabj.v8i1.189 ◽

2016 ◽

Vol 8 (1) ◽

pp. 1 ◽

Cited By ~ 5

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

Immune Cells ◽

Tumor Antigens ◽

Cytotoxic T Lymphocyte ◽

Immune Surveillance ◽

Cancer Therapeutics ◽

Adoptive Cell Transfer ◽

Cell Transfer ◽

Genetically Engineer

BACKGROUND: The goals of treating patients with cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy.CONTENT: During immune surveillance, the host provides defense against foreign antigens, while ensuring it limits activation against self antigens. By targeting surface antigens expressed on tumor cells, monoclonal antibodies have demonstrated efficacy as cancer therapeutics. Recent successful antibody-based strategies have focused on enhancing antitumor immune responses by targeting immune cells, irrespective of tumor antigens. The use of antibodies to block pathways inhibiting the endogenous immune response to cancer, known as checkpoint blockade therapy, has stirred up a great deal of excitement among scientists, physicians, and patients alike. Clinical trials evaluating the safety and efficacy of antibodies that block the T cell inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have reported success in treating subsets of patients. Adoptive cell transfer (ACT) is a highly personalized cancer therapy that involve administration to the cancer-bearing host of immune cells with direct anticancer activity. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment.SUMMARY: For cancer treatment, 2011 marked the beginning of a new era. The underlying basis of cancer immunotherapy is to activate a patient’s own T cells so that they can kill their tumors. Reports of amazing recoveries abound, where patients remain cancer-free many years after receiving the therapy. The idea of harnessing immune cells to fight cancer is not new, but only recently have scientists amassed enough clinical data to demonstrate what a game-changer cancer immunotherapy can be. This field is no stranger to obstacles, so the future looks very promising indeed.KEYWORDS: immune checkpoint, adoptive cell transfer, neoantigen, monoclonal antibody

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Viral platforms for expression of tumor antigens in cancer immunotherapy

Tumor Immunology and Immunotherapy ◽

10.1093/med/9780199676866.003.0015 ◽

2014 ◽

pp. 217-234

Author(s):

Karishma Rajani ◽

Vanessa Alonso-Camino ◽

Nicolas Boisgerault ◽

Richard Vile

Keyword(s):

Cancer Immunotherapy ◽

Tumor Antigens

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Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Cancers ◽

10.3390/cancers12061660 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1660

Author(s):

Sara Feola ◽

Jacopo Chiaro ◽

Beatriz Martins ◽

Vincenzo Cerullo

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

Tumor Antigens ◽

T Cell Response ◽

Antigenic Peptides ◽

T Cell Epitopes ◽

Antigen Discovery ◽

Future Challenges ◽

Major Bottleneck ◽

Therapeutic Cancer Vaccines

According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

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Emerging nanomedicines for effective breast cancer immunotherapy

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00741-z ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Amirhossein Bahreyni ◽

Yasir Mohamud ◽

Honglin Luo

Keyword(s):

Breast Cancer ◽

Immune System ◽

Cancer Immunotherapy ◽

Immune Cells ◽

Tumor Antigens ◽

Host Immune System ◽

Primary Tumors ◽

Novel Approach ◽

Tumor Environment ◽

Advanced Biomaterials

AbstractBreast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side-effects. Here we discuss recent advancements that have been made in nanoparticle-involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

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Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens through Oncolytic Vaccines

Frontiers in Immunology ◽

10.3389/fimmu.2017.00800 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 9

Author(s):

Namit Holay ◽

Youra Kim ◽

Patrick Lee ◽

Shashi Gujar

Keyword(s):

Cancer Immunotherapy ◽

Tumor Antigens

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Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

10.1101/478875 ◽

2018 ◽

Author(s):

Zheng Zhao ◽

Jodi McGill ◽

Mei He

Keyword(s):

Cell Culture ◽

T Cell ◽

Cancer Immunotherapy ◽

Real Time ◽

T Cell Activation ◽

Cell Activation ◽

Tumor Antigens ◽

Parent Cell ◽

Melanoma Tumor ◽

Microfluidic Cell Culture

Extracellular Vesicles (EVs), particularly exosomes (30-150 nm), are an emerging delivery system in mediating cellular communications, which have been observed for priming immune responses by presenting parent cell signaling proteins or tumor antigens to immune cells. Therefore, preparation of antigenic exosomes that can play therapeutic roles, particularly in cancer immunotherapy, is emerging. However, standard benchtop methods (e.g., ultracentrifugation and filtration) lack the ability to purify antigenic exosomes specifically among other microvesicle subtypes, due to the non-selective and time-consuming (>10 h) isolation protocols. Exosome engineering approaches, such as the transfection of parent cells, also suffer from poor yield, low purity, and time-consuming operations. In this paper, we introduce a streamlined microfluidic cell culture platform for integration of harvesting, antigenic modification, and photo-release of surface engineered exosomes in one workflow, which enables the production of intact, MHC peptide surface engineered exosomes for cytolysis activation. The PDMS microfluidic cell culture chip is simply cast from a 3D-printed mold. The proof-of-concept study demonstrated the enhanced ability of harvested exosomes in antigen presentation and T cell activation, by decorating melanoma tumor peptides on the exosome surface (e.g., gp-100, MART-1, MAGE-A3). Such surface engineered antigenic exosomes were harvested in real-time from the on-chip culture of leukocytes isolated from human blood, leading to much faster cellular uptake. The activation of gp100-specific CD8 T cells which were purified from the spleen of 2 Pmel1 transgenic mice was evaluated using surface engineered exosomes prepared from muring antigen presenting cells. Antigen-specific CD8 T cell proliferation was significantly induced by the engineered exosomes compared to native, non-engineered exosomes. This microfluidic platform serves as an automated and highly integrated cell culture device for rapid, and real-time production of therapeutic exosomes that could advance cancer immunotherapy.

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Phage Display as A Bio-Technique for Cancer Immunotherapy

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190611160443 ◽

2020 ◽

Vol 17 (4) ◽

pp. 379-387

Author(s):

Shirin Mahmoodi ◽

Navid Nezafat ◽

Younes Ghasemi

Keyword(s):

Phage Display ◽

Cancer Immunotherapy ◽

Tumor Antigens ◽

High Affinity ◽

Phage Antibodies ◽

Phage Display Libraries ◽

Antigen Presenting ◽

Immunogenic Properties ◽

Specific Peptide ◽

Selection Of

Background: Phage display is a biotechnological technique that presents peptides with coated proteins on the surface of phage. In the last two decades, growing applications of phage display in various fields of biotechnology have been investigated. Phage display libraries allow to present billions of peptides on phage surface for selection of a specific peptide with the desired affinity. Objective: In this regard, high-affinity phage antibodies against tumor antigens are produced and applied for diagnosis and treatment of cancer. Method: Moreover, phage display libraries are employed to select the high affinity T Cell Receptors (TCRs) for the peptide-MHC complex which is an attractive approach in cancer immunotherapy. Due to immunogenic properties of phage particles, phage-based vaccines do not require adjuvant, in addition the phage particles can effectively take up by Antigen Presenting Cells (APCs). Results: Taken together, phage-based cancer vaccines are ideal candidates that provide a key for eradication of tumor cells. Conclusion: In this review, we focus on various applications of a phage display platform in different types of cancer immunotherapy approaches.

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Biogenic particles can be multiantigenic, immunostimulative and activate innate immunity while suppressing tumor development

10.31219/osf.io/q2kby ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Innate Immunity ◽

Immune System ◽

Cancer Immunotherapy ◽

Cancer Vaccines ◽

Tumor Antigens ◽

Critical Role ◽

Tumor Development ◽

Host Cells ◽

Delivery Technique ◽

Biogenic Nanoparticles

Cancer immunotherapy, which attempts to activate or stimulate the immune system to treat cancer, has become the standard of treatment. Although some cancer vaccines are efficiently translated, they have not yet reached the same degree of success as infectious disease immunizations. A primary factor is the low immunogenicity of the tumor and related antigens. Unlike viruses, cancer cells emerge from somatic mutations in patients' healthy tissues, making it harder for the immune system to properly detect tumor cells. Biogenic nanoparticles have recently been highlighted as a solution to address some of the issues with creating anticancer vaccinations. Antigens, medication delivery, and others all benefit from biogenic nanoparticles. Biogenic nanoparticles have long been researched as a vaccine. Biogenic nanoparticles-based platforms, like particular VLPs, inherently activate inflammatory responses and may be increased with TAAs evaluated for antigen-specific antitumor responses to patient malignancies. OMVs and OMV-coated nanoparticles can be multiantigenic and immunostimulative in the box. PAMPs present in OMVs can activate innate immunity while suppressing tumor development. A range of cells, including immune and malignant cells, produce exosomes and play a critical role in cell-to-cell communication. Exosomes may contain interesting materials such as specific drugs, proteins, DNA, and RNA species, and their function depends on host cells. In cancer vaccines, however, these biogenic nanoparticles still have some limitations. Transferring tumor antigens and adjuvants to the secondary lymphoid system is a critical issue for biogenic nanoparticles. OMVs lack tumor antigens. Adjuvants are low in VLPs and exosomes. Furthermore, enhancing the protective response of biogenic nanoparticles, generating protective antigens in these nanoparticles and reducing the toxicity of nanoparticles are all challenges in cancer immunotherapy. There has been a lot of information regarding biogenic nanoparticles created by a variety of bacteria or cells in the area of bacterial vesicle research for a long time, but there has been a dearth of in-depth study focused on identifying molecules crucial to biogenesis or biogenic nanoparticles. Many basic questions remain unanswered here. Which envelope factors release biogenic nanoparticles? What signals and mechanisms regulate biogenic biogenic nanoparticles? Understanding these and other concepts as a cancer immunotherapy delivery technique is vital for the future development of biogenic nanoparticles. Future investigations are anticipated to begin to address these fundamental issues and increase our knowledge.

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