Neoantigen cancer vaccines:a new star on the horizon

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

mRNA vaccines:a new era in vaccine development

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment.mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune system.These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant cells.This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients.Recent breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in oncology.The mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic intervention.Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and efficacy.Pioneering candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,respectively.These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses.While the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption.The development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer vaccines.Overall,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.As research progresses,addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice,offering new hope for patients in the fight against cancer.

Study on the Knowledge of Mothers or Guardians of Girls Aged 9 - 14 from the Langue de Barbarie in Saint-Louis, Senegal about Cervical Cancer and Its Relationship to HPV Vaccination in 2024

Introduction: The relationship between knowledge of HPV and vaccination has been established. The aim of this study was to investigate the knowledge of mothers or guardians of girls aged 9 - 14 about cervical cancer and their attitudes to HPV vaccination. Methodology: This was a descriptive cross-sectional survey. The sample size was calculated using the Schwartz formula and distributed proportionally to the size of the neighbourhood population. Data was collected between 2nd to 19th January 2024 using anonymous questionnaires configured on tablets with Survey 123 software and analysed using R software. Results: A total of 799 people were interviewed. The average age of the respondents was 35.67 years, with a standard deviation of 7.08 and a range of 17 and 49 years. The information channels for cervical cancer were the media (82.8%), health facilities (47.7%) and community intermediaries (23.3%). Only 53.7% had information about the vaccine and 25.5% about the vaccination strategy. The main reason for accepting the vaccine was awareness of the seriousness of cervical cancer (55.1%). Conclusion: It is essential to take stock of knowledge about cervical cancer and attitudes to vaccination to assess the impact of interventions and redirect strategies to improve vaccination coverage. .

Development of therapeutic cancer vaccines using nanomicellar preparations

Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases:State-of-the-art

Although the coronavirus disease 2019(COVID-19)pandemic was declared to be no longer“a public health emergency of international concern”with its wide range of clinical manifestations and late complications,severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat,especially to the elderly and patients with comorbidities.Patients with oncologic diseases are vulnerable to severe infection and death.Indeed,patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity.Unfortunately,cancer patients are usually excluded from vaccine trials and investigations of post-vaccinal immune responses and the effectiveness of the vaccines.We aimed to elucidate to what extent patients with cancer are at increased risk of developing severe COVID-19 and what is their overall case fatality rate.We also present the current concept and evidence on the effectiveness and safety of COVID-19 vaccines,including boosters,in oncology patients.In conclusion,despite the considerably higher mortality in the cancer patient group than the general population,countries with high vaccination rates have demonstrated trends toward improved survival of cancer patients early and late in the pandemic.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

Immunotherapy and therapeutic vaccines in prostate cancer： an update on current strategies and clinical implications

In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleuceI-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

Advances in inducing adaptive immunity using cell-based cancer vaccines: clinical applications in pancreatic cancer

The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

Recent advances in heat shock protein-based cancer vaccines

BACKGROUND: Active immunotherapy has been successful in preventing many infectious diseases, and is being explored for its anti-tumor use. Purified antigens, peptides, gene-based systems and antigens contained in whole cells or cell lysates are used in specific active immunotherapy for cancer, known as cancer vaccines. Cancer vaccines do not directly kill tumor cells, but prime a specific humoral and/or cellular immune response against the tumor. Up to date, many kinds of cancer vaccines have been tested in the world and have shown their own advantages. Heat shock protein (HSP)-based cancer vaccine is one of the outstanding representatives. In this paper, we review recent advances in HSP-based cancer vaccines. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on HSP, cancer vaccines and other related subjects. RESULTS: Several kinds of HSP-based cancer vaccines which have been explored worldwide, include tumor derived HSP-pepdde complex cancer vaccines, artificially reconstituted HSP-peptide complex cancer vaccines, HSPpeptide fusion protein cancer vaccines and HSP-based DNA cancer vaccines, etc. Many HSP-based cancer vaccines are being tested in clinical trials, and some are being tested in phase Ⅲ clinical trials at present. CONCLUSION: The available results in preclinical tests and clinical trials indicate that HSP-based cancer vaccines are promising in cancer therapy.

Personalized pancreatic cancer therapy:from the perspective of mRNA vaccine

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.

Uptake of Two Doses of HPV Vaccines in Nakuru County, Kenya: A Case of Rongai and Nakuru West Sub-Counties

Background: HPV vaccines were introduced globally as one of the most effective strategies to prevent cervical cancer. HPV vaccines were rolled out in Kenya in 2019 targeting girls aged 10 - 14 years, but the uptake has not been satisfactory. The Purpose of the Study: The aim of the study was to assess the level of HPV uptake among girls aged 10 - 14 years in Rongai and Nakuru West Sub-Counties in Nakuru County. Method: This was a cross-sectional study where data on HPV uptake was retrieved from all the public health facilities located in Rongai and Nakuru West Sub-Counties, Nakuru County, entered into Microsoft Excel then transferred to SPSS version 26 for analysis of HPV vaccine uptake since the year 2019 to June 2022. Data Analysis: Descriptive statistics were used where tables and graphs were generated to represent the percentages and trends of HPV vaccine uptake. Results: The average percentage of HPV uptake in Nakuru West Sub-County since the rollout of vaccination was 17% while that of Rongai Sub-County was 15%. In 2019, HPV 1 uptake was generally low for both Sub-Counties, the results show no HPV 2 vaccines were administered during that year. In 2020, Nakuru West reported an increase in HPV 1 uptake, while Rongai reported a drop in HPV 1 uptake. Both Sub-Counties reported an increase in HPV 2 in 2020 as compared to the previous year. The highest HPV 1 & 2 uptakes were reported in 2021 in both Sub-Counties. The uptake of both HPV 1 & 2 kept increasing subsequently. Conclusion: The overall uptake of HPV vaccines for Doses 1 and 2, in both Rongai and Nakuru West Sub-Counties, is low. However, there has been a consistent increase in uptake of the two doses in the two Sub-Counties since 2019. Therefore, raising public awareness of the importance of HPV vaccination could improve uptake.

Cervical Cancer Prevention Challenges and Barriers to Cervical Cancer Screening and HPV Vaccinations in Ukraine and Eastern Europe

Objectives: To identify the obstacles and issues that hinder effective cancer prevention efforts in Ukraine. The study aims to provide a comprehensive assessment of the barriers to cancer prevention, including both infrastructure and behavioral factors, and identify potential solutions to address these challenges. Study Design: Comprehensive literature review. Methods: The following databases were searched: National Center for Biotechnology Information (NCBI) and PubMed (U.S. National Library of Medicine at the National Institutes of Health). The keywords used in the search included “Cervical Cancer”, “Human Papillomavirus Vaccination (HPV)”, “Ukraine”, “Eastern Europe”, “Healthcare Infrastructure in Disasters”, “Cervical Cancer Prevention”, “Pap Smear”, and “HPV Testing”. Results: A total of 3500 articles were screened. A total of 65 articles met the inclusion criteria. Limited public awareness and limited access to vaccination and screening, combined with inadequate treatment facilities lead to higher rates of cervical cancer. The COVID pandemic, war with Russia, and the Chernobyl disaster are significant factors for the low level of vaccination in Ukraine. Conclusion: The prevention and treatment of cervical cancer in Ukraine face significant challenges due to the inadequate HPV vaccination rates and screening by cytology. Efforts to improve funding and increase education of both the population and health care providers are necessary to increase interventions such as HPV vaccination, cervical cytology, and HPV testing to reduce cervical cancer rates in Ukraine.

Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

AIM： To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS： The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems. The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes＇ proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS： The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes＇ proliferations were remarkably increased than their parental dendritic cells. CONCLUSION： The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

Fueling the engine and releasing the break: combinational therapy of cancer vaccines and immune checkpoint inhibitors

Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-ceU infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

Cyclooxygenase Inhibition in Cancer Immunotherapy: Combination of Indomethacin with Cancer Vaccines Is Not Always Beneficial

Cyclooxygenase (COX)-1, but preferable COX-2 catalyzes the synthesis of PGE2 in several tumors, promoting angiogenesis and a suppressive inflammation in their microenvironments. Different types of cancer vaccines have been combined with COX-2 inhibitors, assuming that its particular mechanism of action will not influence the overall results of the combination. In this research, a possible relationship between the type of cancer vaccine and the outcome of the combination with a COX inhibitor was experimentally addressed. We investigated whether nonsteroidal anti-inflammatory drugs (NSAIDs) affect the immune response to vaccination. Three adjuvants were evaluated for humoral and cellular response using ovalbumin (OVA) as antigen. We evaluated also the impact of indomethacin in five tumor models and the correlation of this effect with the secretion of prostaglandin E2 (PGE2) of these cells. We finally studied the combination of indomethacin with two cancer vaccines in three different experimental settings. COX inhibitor did not interfere with dendritic cells maturation in vitro and did not affect the frequency of splenic immune cell populations in mice. However, the induction of OVA-specific antibodies is affected by the COX inhibitor but its impact on cytotoxic CD8+ T cell response is adjuvant-dependent. In contrast, the antitumor effect of the COX inhibitor in the 3LL-D122 tumor model is not mediated by CD4+ or CD8+ T cells. Interestingly, the in vivo effect observed in this model and others didn’t correlate with levels of PGE2 secretion by the tumor cell lines in vitro. Finally, the combination of a COX inhibitor with cancer vaccines may depend on the type of the cancer vaccine.

Bacterial outer membrane vesicle-based cancer nanovaccines

Tumor vaccines,a type of personalized tumor immunotherapy,have developed rapidly in recent decades.These vaccines evoke tumor antigen-specific T cells to achieve immune recognition and killing of tumor cells.Because the immunogenicity of tumor antigens alone is insufficient,immune adjuvants and nanocarriers are often required to enhance anti-tumor immune responses.At present,vaccine carrier development often integrates nanocarriers and immune adjuvants.Among them,outer membrane vesicles(OMVs)are receiving increasing attention as a delivery platform for tumor vaccines.OMVs are natural nanovesicles derived from Gramnegative bacteria,which have adjuvant function because they contain pathogen associated molecular patterns.Importantly,OMVs can be functionally modified by genetic engineering of bacteria,thus laying a foundation for applications as a delivery platform for tumor nanovaccines.This review summarizes 5 aspects of recent progress in,and future development of,OMV-based tumor nanovaccines:strain selection,heterogeneity,tumor antigen loading,immunogenicity and safety,and mass production of OMVs.

Nanoparticle cancer vaccines:Design considerations and recent advances

Vaccines therapeutics manipulate host’s immune system and have broad potential for cancer prevention and treatment.However,due to poor immunogenicity and limited safety,fewer cancer vaccines have been successful in clinical trials.Over the past decades,nanotechnology has been exploited to deliver cancer vaccines,eliciting longlasting and effective immune responses.Compared to traditional vaccines,cancer vaccines delivered by nanomaterials can be tuned towards desired immune profiles by(1)optimizing the physicochemical properties of the nanomaterial carriers,(2)modifying the nanomaterials with targeting molecules,or(3)co-encapsulating with immunostimulators.In order to develop vaccines with desired immunogenicity,a thorough understanding of parameters that affect immune responses is required.Herein,we discussed the effects of physicochemical properties on antigen presentation and immune response,including but not limited to size,particle rigidity,intrinsic immunogenicity.Furthermore,we provided a detailed overview of recent preclinical and clinical advances in nanotechnology for cancer vaccines,and considerations for future directions in advancing the vaccine platform to widespread anti-cancer applications.

The Changes in the Awareness of Cervical Cancer Prevention and the Acceptability of HPV Vaccines among Women after Their Introduction in China

Cervical cancer is a form of malignant tumor that seriously threatens women’s health. In China,according to the cancer statistics, 98,900 new cervical cancer cases and 30,500 deaths due to cervical cancer were estimated to have occurred in2015, and the incidence and mortality rates still exhibited an upward trend[1].

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.