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Molecular Cancer Feb 2021mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in... (Review)
Review
mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.
Topics: Animals; COVID-19; COVID-19 Vaccines; Cancer Vaccines; Humans; Immunotherapy; Neoplasms; SARS-CoV-2; Vaccines, Synthetic; Vaccinology; mRNA Vaccines
PubMed: 33632261
DOI: 10.1186/s12943-021-01335-5 -
Targeted Oncology Mar 2021There are strong biologic and preclinical rationales for the development of therapeutic cancer vaccines; however, the clinical translation of this treatment strategy has... (Review)
Review
There are strong biologic and preclinical rationales for the development of therapeutic cancer vaccines; however, the clinical translation of this treatment strategy has been challenging. It is now understood that many previous clinical trials of cancer vaccines used target antigens or vaccine designs that inherently lacked sufficient immunogenicity to induce clinical responses. Despite the historical track record, breakthrough advances in cancer immunobiology and vaccine technologies have supported continued interest in therapeutic cancer vaccinations, with the hope that next-generation vaccine strategies will enable patients with cancer to develop long-lasting anti-tumor immunity. There has been substantial progress identifying antigens and vaccine vectors that lead to strong and broad T cell responses, tailoring vaccine designs to achieve optimal antigen presentation, and finding combination partners employing complementary mechanisms of action (e.g., checkpoint inhibitors) to overcome the diverse methods cancer cells use to evade and suppress the immune system. Results from randomized, phase 3 studies testing therapeutic cancer vaccines based on these advances are eagerly awaited. Here, we summarize the successes and failures in the clinical development of cancer vaccines, address how this historical experience and advances in science and technology have shaped efforts to improve vaccines, and offer a clinical perspective on the future role of vaccine therapies for cancer.
Topics: Cancer Vaccines; Humans; Neoplasms
PubMed: 33512679
DOI: 10.1007/s11523-020-00788-w -
Frontiers in Immunology 2022Immunotherapy has emerged as a breakthrough strategy in cancer treatment. mRNA vaccines are an attractive and powerful immunotherapeutic platform against cancer because... (Review)
Review
Immunotherapy has emerged as a breakthrough strategy in cancer treatment. mRNA vaccines are an attractive and powerful immunotherapeutic platform against cancer because of their high potency, specificity, versatility, rapid and large-scale development capability, low-cost manufacturing potential, and safety. Recent technological advances in mRNA vaccine design and delivery have accelerated mRNA cancer vaccines' development and clinical application. In this review, we present various cancer vaccine platforms with a focus on nucleic acid vaccines. We discuss rational design and optimization strategies for mRNA cancer vaccine development. We highlight the platforms available for delivery of the mRNA vaccines with a focus on lipid nanoparticles (LNPs) based delivery systems. Finally, we discuss the limitations of mRNA cancer vaccines and future challenges.
Topics: Humans; Cancer Vaccines; Neoplasms; Immunotherapy; RNA, Messenger; mRNA Vaccines
PubMed: 36591226
DOI: 10.3389/fimmu.2022.1029069 -
Proceedings of the National Academy of... Aug 2022The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted...
The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8 T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen-bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2)-encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model when combined with anti-programmed death-1 (PD-1) therapy, revealing broad application of 113-O12B from protein to peptide antigens. All the treated mice showed long-term immune memory, hindering the occurrence of tumor metastatic nodules in the lung in the rechallenging experiments that followed. The enhanced antitumor efficacy of the LN-targeting LNP system shows great potential as a universal platform for the next generation of mRNA vaccines.
Topics: Amino Alcohols; Animals; Antigens; CD8-Positive T-Lymphocytes; Cancer Vaccines; Decanoates; Immunologic Memory; Liposomes; Lymph Nodes; Mice; Nanoparticles; Neoplasm Metastasis; Neoplasms; Ovalbumin; mRNA Vaccines
PubMed: 35969778
DOI: 10.1073/pnas.2207841119 -
Journal of Hematology & Oncology Mar 2022Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is... (Review)
Review
Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc. Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.
Topics: Antigens, Neoplasm; Cancer Vaccines; Humans; Immunity, Cellular; Immunotherapy; Neoplasms
PubMed: 35303904
DOI: 10.1186/s13045-022-01247-x -
Clinical and Translational Medicine Aug 2023Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious... (Review)
Review
Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisition. In this review, we elaborated on the development of cancer vaccines and mRNA cancer vaccines, as well as the potential biological mechanisms of mRNA cancer vaccines and the latest progress in various tumour treatments, and discussed the challenges and future directions for the field.
Topics: Humans; Cancer Vaccines; RNA, Viral; COVID-19; SARS-CoV-2; COVID-19 Vaccines; mRNA Vaccines; Neoplasms
PubMed: 37612832
DOI: 10.1002/ctm2.1384 -
Journal of Immunology Research 2020Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack... (Review)
Review
Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack the cancer cells. These treatments can cure cancer at earlier stages but are frequently ineffective for treating cancer in the advanced or recurrent stages. Basic and clinical research on the tumor microenvironment, which consists of cancerous, stromal, and immune cells, demonstrates the critical role of antitumor immunity in cancer development and progression. Cancer immunotherapies have been proposed as the fourth cancer treatment. In particular, clinical application of immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, in various cancer types represents a major breakthrough in cancer therapy. Nevertheless, accumulating data regarding immune checkpoint inhibitors demonstrate that these are not always effective but are instead only effective in limited cancer populations. Indeed, several issues remain to be solved to improve their clinical efficacy; these include low cancer cell antigenicity and poor infiltration and/or accumulation of immune cells in the cancer microenvironment. Therefore, to accelerate the further development of cancer immunotherapies, more studies are necessary. In this review, we will summarize the current status of cancer immunotherapies, especially cancer vaccines, and discuss the potential problems and solutions for the next breakthrough in cancer immunotherapy.
Topics: Animals; Biomarkers; Cancer Vaccines; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunotherapy; Neoplasms; Treatment Outcome; Tumor Escape
PubMed: 33282961
DOI: 10.1155/2020/5825401 -
Journal of Hematology & Oncology Sep 2021Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was... (Review)
Review
Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.
Topics: Animals; Cancer Vaccines; Combined Modality Therapy; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Oncolytic Virotherapy
PubMed: 34579759
DOI: 10.1186/s13045-021-01164-5 -
Military Medical Research Oct 2022Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity, especially in genetic alteration and microenvironment. Conventional therapeutic... (Review)
Review
Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity, especially in genetic alteration and microenvironment. Conventional therapeutic strategies for pancreatic cancer usually suffer resistance, highlighting the necessity for personalized precise treatment. Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting, minimal nonspecific effects, broad therapeutic window, low toxicity, and induction of persistent immunological memory. Multiple conventional vaccines based on the cells, microorganisms, exosomes, proteins, peptides, or DNA against pancreatic cancer have been developed; however, their overall efficacy remains unsatisfactory. Compared with these vaccine modalities, messager RNA (mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment, and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer. This review summarizes the current progress on pancreatic cancer vaccines, highlights the superiority of mRNA vaccines over other conventional vaccines, and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
Topics: Cancer Vaccines; Humans; Pancreatic Neoplasms; Peptides; RNA; RNA, Messenger; Tumor Microenvironment; Vaccines, Synthetic; mRNA Vaccines
PubMed: 36224645
DOI: 10.1186/s40779-022-00416-w -
Frontiers in Immunology 2022Breast cancer has become the most commonly diagnosed cancer globally. The relapse and metastasis of breast cancer remain a great challenge despite advances in... (Review)
Review
Breast cancer has become the most commonly diagnosed cancer globally. The relapse and metastasis of breast cancer remain a great challenge despite advances in chemotherapy, endocrine therapy, and HER2 targeted therapy in the past decades. Innovative therapeutic strategies are still critically in need. Cancer vaccine is an attractive option as it aims to induce a durable immunologic response to eradicate tumor cells. Different types of breast cancer vaccines have been evaluated in clinical trials, but none has led to significant benefits. Despite the disappointing results at present, new promise from the latest study indicates the possibility of applying vaccines in combination with anti-HER2 monoclonal antibodies or immune checkpoint blockade. This review summarizes the principles and mechanisms underlying breast cancer vaccines, recapitulates the type and administration routes of vaccine, reviews the current results of relevant clinical trials, and addresses the potential reasons for the setbacks and future directions to explore.
Topics: Antigens, Neoplasm; Breast Neoplasms; Cancer Vaccines; Drug Delivery Systems; Drug Therapy, Combination; Female; Humans; Immunotherapy; Randomized Controlled Trials as Topic; Receptor, ErbB-2
PubMed: 35154149
DOI: 10.3389/fimmu.2022.828386