scholarly journals Anti-Cancer Immunotherapies Targeting Telomerase

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2260
Author(s):  
Simone Negrini ◽  
Raffaele De Palma ◽  
Gilberto Filaci
Keyword(s):  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Human Leukocyte ◽  
Clinical Settings ◽  
Leukocyte Antigen ◽  
Tumor Associated Antigen ◽  
Anti Cancer ◽  
Recent Developments ◽  
Human Telomerase ◽  
Cancer Immunotherapies

Telomerase is a reverse transcriptase that maintains telomeres length, compensating for the attrition of chromosomal ends that occurs during each replication cycle. Telomerase is expressed in germ cells and stem cells, whereas it is virtually undetectable in adult somatic cells. On the other hand, telomerase is broadly expressed in the majority of human tumors playing a crucial role in the replicative behavior and immortality of cancer cells. Several studies have demonstrated that telomerase-derived peptides are able to bind to HLA (human leukocyte antigen) class I and class II molecules and effectively activate both CD8+ and CD4+ T cells subsets. Due to its broad and selective expression in cancer cells and its significant immunogenicity, telomerase is considered an ideal universal tumor-associated antigen, and consequently, a very attractive target for anti-cancer immunotherapy. To date, different telomerase targeting immunotherapies have been studied in pre-clinical and clinical settings, these approaches include peptide vaccination and cell-based vaccination. The objective of this review paper is to discuss the role of human telomerase in cancer immunotherapy analyzing recent developments and future perspectives in this field.

scholarly journals Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies

2020 ◽  
Vol 5 ◽  
pp. 14-14
Author(s):  
Chenwei Wang ◽  
Chengjie Xiong ◽  
Yung-Chun Hsu ◽  
Xiaoling Wang ◽  
Lin Chen
Keyword(s):  
Human Leukocyte Antigen ◽  
Cancer Immunotherapy ◽  
Human Leukocyte ◽  
Leukocyte Antigen

scholarly journals Advances in Engineered Polymer Nanoparticle Tracking Platforms towards Cancer Immunotherapy—Current Status and Future Perspectives

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 935
Author(s):  
Ramar Thangam ◽  
Kapil D. Patel ◽  
Heemin Kang ◽  
Ramasamy Paulmurugan
Keyword(s):  
Cancer Immunotherapy ◽  
Anticancer Agents ◽  
Polymeric Nanoparticles ◽  
Current Status ◽  
Polymeric Nanocarriers ◽  
Therapeutic Drugs ◽  
Small Molecule Ligands ◽  
Recent Developments ◽  
Cancer Immunotherapies

Engineering polymeric nanoparticles for their shape, size, surface chemistry, and functionalization using various targeting molecules has shown improved biomedical applications for nanoparticles. Polymeric nanoparticles have created tremendous therapeutic platforms, particularly applications related to chemo- and immunotherapies in cancer. Recently advancements in immunotherapies have broadened this field in immunology and biomedical engineering, where “immunoengineering” creates solutions to target translational science. In this regard, the nanoengineering field has offered the various techniques necessary to manufacture and assemble multifunctional polymeric nanomaterial systems. These include nanoparticles functionalized using antibodies, small molecule ligands, targeted peptides, proteins, and other novel agents that trigger and encourage biological systems to accept the engineered materials as immune enhancers or as vaccines to elevate therapeutic functions. Strategies to engineer polymeric nanoparticles with therapeutic and targeting molecules can provide solutions for developing immune vaccines via maintaining the receptor storage in T- and B cells. Furthermore, cancer immunotherapy using polymeric nanomaterials can serve as a gold standard approach for treating primary and metastasized tumors. The current status of the limited availability of immuno-therapeutic drugs highlights the importance of polymeric nanomaterial platforms to improve the outcomes via delivering anticancer agents at localized sites, thereby enhancing the host immune response in cancer therapy. This review mainly focuses on the potential scientific enhancements and recent developments in cancer immunotherapies by explicitly discussing the role of polymeric nanocarriers as nano-vaccines. We also briefly discuss the role of multifunctional nanomaterials for their therapeutic impacts on translational clinical applications.

scholarly journals Deciphering Human Leukocyte Antigen Susceptibility Maps From Immunopeptidomics Characterization in Oncology and Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Pablo Juanes-Velasco ◽  
Alicia Landeira-Viñuela ◽  
Vanessa Acebes-Fernandez ◽  
Ángela-Patricia Hernández ◽  
Marina L. Garcia-Vaquero ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
High Sensitivity ◽  
Hla Typing ◽  
Mhc I ◽  
Vaccination Programs ◽  
Leukocyte Antigen ◽  
Immunogenic Peptides ◽  
Susceptibility Maps ◽  
Recent Developments

Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to many diseases such as cancer, auto-immune or infectious diseases. Individual genetic variation may help to explain different immune responses to microorganisms across a population. HLA typing can be fast and inexpensive; however, deciphering peptides loaded on MHC-I and II which are presented to T cells, require the design and development of high-sensitivity methodological approaches and subsequently databases. Hence, these novel strategies and databases could help in the generation of vaccines using these potential immunogenic peptides and in identifying high-risk HLA types to be prioritized for vaccination programs. Herein, the recent developments and approaches, in this field, focusing on the identification of immunogenic peptides have been reviewed and the next steps to promote their translation into biomedical and clinical practice are discussed.

scholarly journals Overcoming the problem of the lack of an immune response to cancer: A possible haptogenic approach to cancer immunotherapy

2021 ◽  
Vol 5 (1) ◽  
pp. 01-04
Author(s):  
Patrick Riley
Keyword(s):  
Immune Response ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Immunological Response ◽  
Gene Products ◽  
Malignant Cells ◽  
Deviant Behaviour ◽  
Anti Cancer ◽  
Immune Response To Cancer ◽  
Normal Gene

Cancer cells possess a number of unusual features, most of which are explicable in the light of the theory of epigenetic carcinogenesis. This includes the remarkable failure of malignant cells to evoke an immunological response from the host which is ascribed to their deviant behaviour resulting from anomalous expression of normal gene products. Given this background a possible approach to eliciting a specific anti-cancer immune response is proposed which involves selective haptenation of an identifiable target protein.

scholarly journals CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens

2020 ◽  
pp. mcp.RA120.002201
Author(s):  
Greta Forlani ◽  
Justine Michaux ◽  
HuiSong Pak ◽  
Florian Huber ◽  
Elodie Lauret Marie Joseph ◽  
...  
Keyword(s):  
Cell Lines ◽  
Tumor Antigens ◽  
Therapeutic Potential ◽  
Human Leukocyte ◽  
Class Ii ◽  
Leukocyte Antigen ◽  
Hla Ligands ◽  
Tumor Types ◽  
Antigen Presenting ◽  
Cancer Immunotherapies

CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17 and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared to interferon gamma (IFNɣ) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor-antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.

Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1505-1512 ◽  
Author(s):  
Gilberto Filaci ◽  
Marco Fravega ◽  
Maurizio Setti ◽  
Paolo Traverso ◽  
Enrico Millo ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Ex Vivo ◽  
Human Leukocyte ◽  
High Rate ◽  
Leukocyte Antigen ◽  
Patients With Cancer ◽  
Cd8 T Lymphocytes ◽  
Tumor Associated Antigen ◽  
Study Support ◽  
Immunologic Status

Telomerase is considered a universal tumor-associated antigen (TAA) due to its high rate of expression by cancers (≈90%), and clinical trials are in progress to test the immunotherapeutical efficacy of antitelomerase immunization in patients with cancer. However, the data concerning frequency and functional activity of telomerase-specific cytotoxic T lymphocytes (CTLs) in patients with cancer are few and conflicting, although their knowledge would be mandatory to predict the efficacy of telomerase-specific immunotherapy in selected patients. We performed this study to analyze frequency and cytolytic function of circulating CD8+ T lymphocytes specific for the p540 telomerase peptide in a series of human leukocyte antigen (HLA)–A2+ cancer patients. The results show that most patients with cancer have circulating telomerase-specific CD8+ T lymphocytes, but a high frequency of telomerase-specific CTLs are present only in a fraction of them. Furthermore, CTL lines able to kill telomerase-positive tumor cells, including autologous cancer cells, can be expanded ex vivo from some, but not all, patients with cancer. In conclusion, the results of the study support the development of clinical protocols using telomerase peptides as an immunizing agent. However, they underline the necessity to study single patients immunologically before undergoing vaccination, to select the patients adequately, and to eventually adapt the immunization schedule to the patient's immunologic status.

scholarly journals Antigen Targets for the Development of Immunotherapies in Leukemia

2019 ◽  
Vol 20 (6) ◽  
pp. 1397 ◽  
Author(s):  
Jens Bauer ◽  
Annika Nelde ◽  
Tatjana Bilich ◽  
Juliane Walz
Keyword(s):  
Tumor Antigens ◽  
Human Leukocyte ◽  
Donor Lymphocyte Infusion ◽  
Leukemic Cells ◽  
T Cell Epitopes ◽  
Leukocyte Antigen ◽  
Selection Strategies ◽  
Car T ◽  
Suitable Target ◽  
Cancer Immunotherapies

Immunotherapeutic approaches, including allogeneic stem cell transplantation and donor lymphocyte infusion, have significantly improved the prognosis of leukemia patients. Further efforts are now focusing on the development of immunotherapies that are able to target leukemic cells more specifically, comprising monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and dendritic cell- or peptide-based vaccination strategies. One main prerequisite for such antigen-specific approaches is the selection of suitable target structures on leukemic cells. In general, the targets for anti-cancer immunotherapies can be divided into two groups: (1) T-cell epitopes relying on the presentation of peptides via human leukocyte antigen (HLA) molecules and (2) surface structures, which are HLA-independently expressed on cancer cells. This review discusses the most promising tumor antigens as well as the underlying discovery and selection strategies for the development of anti-leukemia immunotherapies.

scholarly journals Strategies of current cancer immunotherapy

2019 ◽  
Vol 73 ◽  
pp. 898-908
Author(s):  
Zuzanna Rzepka ◽  
Marta Knapik ◽  
Dorota Wrześniok
Keyword(s):  
Cancer Immunotherapy ◽  
Current Knowledge ◽  
Point Of View ◽  
Adoptive Cell Transfer ◽  
Oncolytic Viruses ◽  
Surgical Methods ◽  
Anti Cancer ◽  
New Treatments ◽  
Cancer Immunotherapies ◽  
Significant Health

Cancers are a significant health problem in the world. The most common therapeutic methods applied in oncology are chemotherapy, radiotherapy and surgical methods. Finding new therapies in this branch of medicine, as well as developing solutions with the highest possible effectiveness, taking into account the multifactorial nature of cancer, is important from both the scientific and medical point of view and, for obvious reasons, it is in the interest of many people. Immunotherapy, despite many years of initial failures, has become one of the most important clinically approved new treatments in oncology and is now successfully used in the treatment of certain types of cancer. Current immunotherapeutic strategies are based on monoclonal antibodies (including inhibitors of immune control points), cytokines, anti-cancer vaccines, oncolytic viruses, as well as adoptive cell transfer. For many cancer immunotherapies, an increase in their effectiveness is observed when they are used with other types of immunotherapy as well as in combination with molecular targeted therapy, chemotherapy or radiotherapy. The dynamic development of cancer immunotherapy since the beginning of the 21st century results from the advances in genetic engineering, as well as from the increase in knowledge about the anticancer immune response and the nature of cancer cells including abnormalities in their metabolism, the ability to create a tumor microenvironment and the induction of immunosuppression. The aim of the study is to present current knowledge in the field of cancer immunotherapy strategies.

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