NO ABSTRACT
Author Info: -1
Author Info: -1
Exosome-based cancer vaccine: a cell-free approach
Despite advancements in medical research, cancer remains a significant and persistent cause of death globally. Cancer vaccine, a novel approach, holds immense promise in development of potentially effective cancer treatment. While the concept of developing cancer vaccines has been explored for decades, significant challenges have hindered their clinical translation. Recent researchers have introduced exosomes as the key element for novel cell-free approach of cancer vaccines. Exosomes are a type of extracellular vesicle (EVs) secreted by various cells. These tiny structures can transport and deliver important biomolecules, such as DNA, RNA, proteins, lipids, and immune-stimulatory molecules, to stimulate the body's anti-tumor immune response. Their biocompatibility, targeting ability, immunogenicity, and a notable capacity to cross biological barriers nominate them as promising candidates for cancer vaccine development by addressing current challenges in cancer therapy. This review explores the current state of knowledge on the efficacy of exosomes from various sources for personalized cancer vaccine development, preclinical and clinical evaluations, along with the strategies to optimize immunogenicity and antigen presentation. We also discuss the challenges and potential solutions for overcoming tumor microenvironment-related hurdles, highlighting the promise of exosome-based approaches for cancer immunotherapy by developing a novel cell-free cancer vaccine in future.
Author Info: (1) Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India. (2) Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharash
Author Info: (1) Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India. (2) Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India. (3) Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India. (4) Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia. vetris@sunway.edu.my.
Plasticity of tumor cell immunogenicity: is it druggable
This short perspective presents, at a high level, some observations and speculations about cancer immunotherapy that derive from experiences at the Dana-Farber Cancer Institute and the Novartis Institutes of Biomedical Research.
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA glenn_dranoff@dfci.harvard.edu.
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA glenn_dranoff@dfci.harvard.edu.
Dendritic Cell Cancer Vaccines: Clinical Production for Cancer Immunotherapy
Dendritic cell (DC) cancer vaccines are used to circumvent the problem that DCs in patients with cancer usually do not mature properly in the cancer environment. Peripheral DCs are fewer in number and hard to isolate cleanly. Instead, autologous DCs can be matured from monocyte precursors obtained by apheresis and elutriation from peripheral blood. Here, we describe procedures for harvesting cells, growing them into DCs, inducing antigen expression by pulsing them with antigenic peptides or inducing antigen expression by transducing them with antigens expressed by a recombinant adenovirus (or other viral vector), maturing them in vitro, and then administering them to patients.
Author Info: (1) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. hoyoung.maeng@nih.gov. (2) Vaccine Branch, Center for C
Author Info: (1) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. hoyoung.maeng@nih.gov. (2) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (3) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (4) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (5) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (6) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
CTLA-4-two pathways to anti-tumour immunity
Immune checkpoint inhibitor (ICI) therapies have revolutionized cancer therapy and improved patient outcomes in a range of cancers. ICIs enhance anti-tumour immunity by targeting the inhibitory checkpoint receptors CTLA-4, PD-1, PD-L1, and LAG-3. Despite their success, efficacy, and tolerance vary between patients, raising new challenges to improve these therapies. These could be addressed by the identification of robust biomarkers to predict patient outcome and a more complete understanding of how ICIs affect and are affected by the tumour microenvironment (TME). Despite being the first ICIs to be introduced, anti-CTLA-4 antibodies have underperformed compared with antibodies that target the PD-1/PDL-1 axis. This is due to the complexity regarding their precise mechanism of action, with two possible routes to efficacy identified. The first is a direct enhancement of effector T-cell responses through simple blockade of CTLA-4-'releasing the brakes', while the second requires prior elimination of regulatory T cells (T(REG)) to allow emergence of T-cell-mediated destruction of tumour cells. We examine evidence indicating both mechanisms exist but offer different antagonistic characteristics. Further, we investigate the potential of the soluble isoform of CTLA-4, sCTLA-4, as a confounding factor for current therapies, but also as a therapeutic for delivering antigen-specific anti-tumour immunity.
Author Info: (1) Medical Sciences and Nutrition, Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom. (2) Department of Pharmacology and Therapeu
Author Info: (1) Medical Sciences and Nutrition, Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom. (2) Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom. (3) Medical Sciences and Nutrition, Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom. (4) Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom. (5) Medical Sciences and Nutrition, Institute of Dentistry, School of Medicine, Sciences & Nutrition, University of Aberdeen, Aberdeen, United Kingdom. School of Dentistry, College of Medicine and Health, The University of Birmingham, Birmingham, United Kingdom.
Intrinsic properties of the lymph node render it immunologically susceptible to metastasis
Lymph nodes (LNs) are the staging grounds for anti-tumor immunity, therefore their high susceptibility to metastatic colonization is a paradox. Previous studies have suggested that extrinsic tumor-derived factors precondition the draining LN to enable tumor cell survival by promoting a state of immune suppression. Here, we investigate whether properties of the LN itself may impede its ability to clear metastasizing tumor cells. Using multiple immunocompetent transplant models, we show that LNs possess intrinsic features, independent of preconditioning, which make them an advantageous site for tumor cells to evade T cell control. Tumor growth in the LN is facilitated by regulatory T cells, which locally suppress the cytolytic capacity of tumor-specific CD8 T cells by restricting IL-2. These findings identify an intrinsic mechanism that contributes to the high rate of LN metastasis in solid tumors.
Author Info: (1) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (2) Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States. (3) University
Author Info: (1) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (2) Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States. (3) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (4) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (5) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (6) Qilu Hospital of Shandong University, Jinan, China. (7) University of Pennsylvania, Philadelphia, Pennsylvania, United States. (8) Huazhong University of Science and Technology, Wuhan, China. (9) Memorial Sloan Kettering Cancer Center, New York, NY, United States. (10) University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Dendritic Cell Cancer Vaccines: A Focused Review
Dendritic cells (DCs) are the most potent professional antigen-presenting cells to activate both CD4+ and CD8+ T lymphocytes. When immature, they take up and process antigens efficiently. When mature, they express high levels of MHC class I and II molecules and costimulatory molecules on their surface and secrete both IL-12 and IL-15 that can activate and steer T cells. However, in patients with cancer or tumor-bearing animals, cancers secrete cytokines that suppress DC development or maturation. To circumvent this barrier to immunization against cancer, strategies have been developed to grow and mature DCs ex vivo from precursors, such as peripheral blood monocytes or bone marrow precursors, induce expression of tumor antigens ex vivo, and then administer the autologous DCs to the patient as a vaccine. The DCs may be coated with synthetic antigenic peptides or transduced with a virus expressing the tumor antigen (see Note 1). Both of these have been used in early clinical trials with promising immunogenicity. Such cancer vaccines may be especially critical for "cold" tumors that do not induce a sufficient immune response by themselves to be amenable to checkpoint inhibitor therapy or blockade of other negative regulators of immunity but with a cancer vaccine to induce the immune response, may become responsive to such immunotherapies. Conversely, cancer vaccines should become more effective if immunosuppressive mechanisms are blocked. Thus, the two approaches should synergize to optimize anticancer immune responses and reject the cancer like an allogeneic organ transplant.
Author Info: (1) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. hoyoung.maeng@nih.gov. (2) Vaccine Branch, Center for C
Author Info: (1) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. hoyoung.maeng@nih.gov. (2) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (3) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (4) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (5) Center for Cellular Engineering, Department of Transfusion Medicine, NIH Clinical Center, Bethesda, MD, USA. (6) Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Extracellular vesicles in tumor immunity: mechanisms and novel insights
Extracellular vesicles (EVs), nanoscale vesicles secreted by cells, have attracted considerable attention in recent years due to their role in tumor immunomodulation. These vesicles facilitate intercellular communication by transporting proteins, nucleic acids, and other biologically active substances, and they exhibit a dual role in tumor development and immune evasion mechanisms. Specifically, EVs can assist tumor cells in evading immune surveillance and attack by impairing immune cell function or modulating immunosuppressive pathways, thereby promoting tumor progression and metastasis. Conversely, they can also transport and release immunomodulatory factors that stimulate the activation and regulation of the immune system, enhancing the body's capacity to combat malignant diseases. This dual functionality of EVs presents promising avenues and targets for tumor immunotherapy. By examining the biological characteristics of EVs and their influence on tumor immunity, novel therapeutic strategies can be developed to improve the efficacy and relevance of cancer treatment. This review delineates the complex role of EVs in tumor immunomodulation and explores their potential implications for cancer therapeutic approaches, aiming to establish a theoretical foundation and provide practical insights for the advancement of future EVs-based cancer immunotherapy strategies.
Author Info: (1) School of Medicine, Chongqing University, Chongqing, China. (2) Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China. (3) School of Medicine,
Author Info: (1) School of Medicine, Chongqing University, Chongqing, China. (2) Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China. (3) School of Medicine, Chongqing University, Chongqing, China. lys@cqu.edu.cn. Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China. lys@cqu.edu.cn.
Extracellular Vesicle-Based Antitumor Nanomedicines
Extracellular vesicles (EVs) have emerged as promising bioactive carriers for delivering therapeutic agents, including nucleic acids, proteins, and small-molecule drugs, owing to their excellent physicochemical stability and biocompatibility. However, comprehensive reviews on the various types of EV-based nanomedicines for cancer therapy remain scarce. This review explores the potential of EVs as antitumor nanomedicines. Methods for EV extraction, drug loading, and engineering modifications are systematically examined, and the strengths and limitations of these technical approaches are critically assessed. Additionally, key strategies for developing EV-based antitumor therapies are highlighted. Finally, the opportunities and challenges associated with advancing EVs toward clinical translation are discussed. With the integration of multiple disciplines, robust EV-based therapeutic platforms are expected to be manufactured to provide more personalized and effective solutions for oncology patients.
Author Info: (1) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. (2) Department of Pharmaceutical Enginee
Author Info: (1) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. (2) Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, P. R. China. (3) Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. (4) Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, P. R. China. (5) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. (6) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. (7) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. (8) Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, P. R. China. Molecular Imaging Research Center of Central South University, Changsha, Hunan, 410008, P. R. China.
Cytokine-centered strategies to boost cancer immunotherapy
Cytokines have gained attention in oncology in recent years, especially in the context of immunotherapy. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, there are still some challenges to be faced, such as the lack of predictive biomarkers as well as the emergence of resistance and their severe side effects. In this Viewpoint, we discuss the potential of cytokines, the soluble mediators of cancer-associated inflammation, in immunotherapy. Indeed, both the activation and inhibition of cytokines have been suggested as potential strategies to overcome immunotherapy resistance. In addition, serum levels of certain cytokines can predict response to immunotherapy, and cytokine inhibition could also contribute to prevent side effects induced by ICIs. Thus, although further research is still required, data support that cytokine-based therapies could be an attractive therapeutic strategy for cancer patients treated with immunotherapy in the near future.
Author Info: (1) Biogipuzkoa (previously known as Biodonostia) Health Research Institute, San Sebastin-Donostia, Spain. (2) Biogipuzkoa (previously known as Biodonostia) Health Research Instit
Author Info: (1) Biogipuzkoa (previously known as Biodonostia) Health Research Institute, San Sebastin-Donostia, Spain. (2) Biogipuzkoa (previously known as Biodonostia) Health Research Institute, San Sebastin-Donostia, Spain. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
