Cell Vaccine Research Articles

The frequency and function of nucleoprotein-specific CD8+ T cells are critical for heterosubtypic immunity against influenza virus infection.

Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer.

Characteristics of virus-specific immunological reactions following COVID-19 vaccination in heart transplant recipients

Heart transplant patients are at an increased risk of COVID-19 infection adverse outcomes because of underlying immunosuppression and concomitant comorbidities. To date, all large-scale randomized controlled trials for various COVID-19 vaccines have excluded solid organ transplant recipients. Therefore, the efficacy and safety of coronavirus infection prevention using COVID-19 vaccines in transplant heart patients has not been sufficiently studied. In this research, the evaluation of virus-specific immunological reactions after vaccination (double Vero Cell vaccination and Sputnik Light booster vaccination) in heart transplant patients has been carried out. In vaccinated heart transplant individuals who did not have a history of COVID-19, starting from 4–6 months after the 2nd dose of the vaccine, an increase in antibodies to S protein level of was observed, while maintaining statistically significant differences for 9–12 months after vaccination (regardless of whether with or without booster vaccination). However, the concentration of antibodies remained low, and 37% of patients detected no antibodies. In vaccinated heart transplant individuals following the previous COVID-19 infection, as compared to seronegative patients, post-vaccination immunity is accompanied by maintaining a high level of virus-specific IgG antibodies to the S protein of the SARS-CoV-2 virus in the dynamics of the post-vaccination period with a statistically significant increase of these antibodies by 9–12 months after booster vaccination. The specific cellular response (according to the assessment of CD3⁺154⁺ and CD3⁺IFNγ⁺ TNFα⁺ cells) to the S protein of the SARS-CoV-2 virus remained low throughout the entire follow-up period, was recorded in 5–40% of heart transplant patients and statistically significant changes in the number of spikereactive lymphocytes were observed in patients with a history of COVID-19 by 4–6 months after administration of the 2nd dose of the vaccine. This, together with the results of the assessment of the humoral response, indicates a more pronounced post-vaccination immunity in patients with a hybrid immunity. While developing a methodology for assessing the risk and benefit of a vaccination strategy for individual heart transplant patients, clinical efficacy, ongoing monitoring of rare serious adverse events, and data on vaccine immunogenicity should be taken into account.

Developments and applications of therapeutic tumor vaccines

The incidence and mortality rates of malignant tumors have rapidly increased. Cancer has become the leading cause of death worldwide. Traditional treatment methods such as surgery, chemotherapy, and radiation have limited effectiveness, with poor prognosis, drug resistance, and low specificity. As a result, cancer immunotherapy has emerged as a promising approach in biotechnology. The development and application of tumor vaccines in tumor immunotherapy have garnered significant attention. These vaccines employ TAA or TSA to activate the bodys specific immune response against tumor cells. This review provides an overview of the tumor microenvironment, tumor immunotherapy, and various types of therapeutic cancer vaccines, including peptide, cell, DC, nucleic acid (DNA and mRNA), and neoantigen vaccines. In conclusion, this review summarizes the current progress and future prospects of tumor vaccines.

Efficacy of novel allogeneic cancer cells vaccine to treat colorectal cancer.

Colorectal cancer (CRC) remains a significant global health burden, emphasizing the need for innovative treatment strategies. 95% of the CRC population are microsatellite stable (MSS), insensitive to classical immunotherapies such as anti-PD-1; on the other hand, responders can become resistant and relapse. Recently, the use of cancer vaccines enhanced the immune response against tumor cells. In this context, we developed a therapeutic vaccine based on Stimulated Tumor Cells (STC) platform technology. This vaccine is composed of selected tumor cell lines stressed and haptenated in vitro to generate a factory of immunogenic cancer-related antigens validated by a proteomic cross analysis with patient's biopsies. This technology allows a multi-specific education of the immune system to target tumor cells harboring resistant clones. Here, we report safety and antitumor efficacy of the murine version of the STC vaccine on CT26 BALB/c CRC syngeneic murine models. We showed that one cell line (1CL)-based STC vaccine suppressed tumor growth and extended survival. In addition, three cell lines (3CL)-based STC vaccine significantly improves these parameters by presenting additional tumor-related antigens inducing a multi-specific anti-tumor immune response. Furthermore, proteomic analyses validated that the 3CL-based STC vaccine represents a wider quality range of tumor-related proteins than the 1CL-based STC vaccine covering key categories of tumor antigens related to tumor plasticity and treatment resistance. We also evaluated the efficacy of STC vaccine in an MC38 anti-PD-1 resistant syngeneic murine model. Vaccination with the 3CL-based STC vaccine significantly improved survival and showed a confirmed complete response with an antitumor activity carried by the increase of CD8+ lymphocyte T cells and M1 macrophage infiltration. These results demonstrate the potential of this technology to produce human vaccines for the treatment of patients with CRC.

Bioproduction and immunogenic evaluation of SARS-CoV-2 prototype vaccine in silkworm BmN cells

COVID-19, caused by the novel coronavirus SARS-CoV-2, has presented a significant challenge to global health, security, and the economy. Vaccination is considered a crucial measure in preventing virus transmission. The silkworm bioreactor has gained widespread usage in antigen presentation, monoclonal antibody preparation, and subunit vaccine development due to its safety, efficiency, convenience, and cost-effectiveness. In this study, we employed silkworm BmN cells and the silkworm MultiBac multigene co-expression system to successfully produce two prototype vaccines: a recombinant baculovirus vector vaccine (NPV) co-displaying the SARS-CoV-2 virus capsid protein and a capsid protein virus-like particle (VLP) vaccine. Following the purification of these vaccines, we immunized BALB/c mice to evaluate their immunogenicity. Our results demonstrated that both VLP and NPV prototype vaccines effectively elicited robust immune responses in mice. However, when equal inoculation doses between groups were compared, the recombinant NPV vaccine exhibited significantly higher serum antibody titers and increased expression of spleen cytokines and lymphocyte immune regulatory factors compared to the VLP group. These results suggested an increased immune efficacy of the recombinant NPV vaccine. Conversely, the VLP prototype vaccine displayed more pronounced effects on lymphocyte cell differentiation induction. This study successfully constructed two distinct morphological recombinant vaccine models and systematically elucidated their differences in humoral immune response and lymphocyte differentiation rate. Furthermore, it has fully harnessed the immense potential of silkworm bioreactors for vaccine research and development, providing valuable technical insights for studying mutated viruses like coronaviruses.

Retraction: Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

Retraction: Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Personalized dendritic cell vaccine in multimodal individualized combination therapy improves survival in high-risk pediatric cancer patients.

A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.

Immunogenicity of 4-dose Essen intramuscular regimen for rabies post-exposure prophylaxis: A multi-center cross-sectional study in China

BackgroundThe 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. MethodRabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14–28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. ResultsFinally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). ConclusionsThe 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

Dendritic cell vaccines as cancer treatment: focus on 13 years of manufacturing and quality control experience in advanced therapy medicinal products

Background aimsDendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices. AimsFrom March 2010 to December 2023, 103 patients were enrolled in multiple clinical trials at the Immuno-Gene Therapy Factory at IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”. Six hundred forty-two doses were produced, and the manufacturing process was implemented to optimize production. Our study is a retrospective analysis focusing on the quality control results. MethodsWe retrospectively analyzed the results of the quality control tests carried out on each produced batch, evaluating viability, purity and phenotype of mDCs and their quality in terms of microbiological safety. The data obtained are given with median and interquartile range. ResultsThe batches were found to be microbiologically safe in terms of sterility, mycoplasma, and endotoxins. An increase in DC maturation markers was found. The release criteria checks showed a high percentage of viability and purity was maintained during the production process. ConclusionsOur findings have confirmed that the measures implemented have ensured the safety of the products and have contributed to the establishing a robust “Pharmaceutical Quality System.” This has enabled many safe mDCs to be produced for clinical trials.

Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case.

Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial. A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality. The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112.

Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]

A first-in-human study to evaluate a personalized neoantigen-based mRNA-loaded dendritic cell vaccine, in combination with ablation, in patients with hepatocellular carcinoma.

e14513 Background: Local recurrence of Hepatocellular Carcinoma (HCC) following potentially curative resection or ablation is an inevitable risk. T cells recognizing neoantigens are present in most cancers including HCC and offer a specific and highly immunogenic target for the personalized vaccination as an adjuvant therapy. The purpose of this study is to evaluate the safety and T cell immune response of a personalized neoantigen-based mRNA loaded dendritic cell (DC) vaccine (LK101) combined with regular ablation in patients with HCC (NCT03674073). Methods: Each patient’s fresh tumor biopsy and matched peripheral blood sample were subjected to whole-exome sequencing and RNA-sequencing. Following determination of somatic mutations and gene expression, up to 30 in silico–predicted potential neoantigens were selected with bioinformatic tool. DCs were generated from the monocytes enriched by leukapheresis, followed by transfection with neoantigen-encoding mRNA through electroporation. In total, 7 doses of LK101 were administered at 1.5×107 cells/injection intradermally with 4-dose priming weekly and 3 boosters in 4-week intervals. The primary endpoint of the clinical study was safety, and key secondary endpoints were immunogenicity, overall survival and recurrence. 24 HCC patients at HKLC stage IIa were enrolled 1:1 to ablation control arm and ablation combined with DC (LK101) arm. Results: The study was completed, patients were followed up for a median of 48.4 months and 38.8 months in vaccination arm and control arm. All of adverse events were Grade 1-2. Most frequent treatment-related adverse events are injection site reactions, inclusive of local pain (63.6%), itch (27.3%) and others (27.3%), such as redness and edema. 3 patients in ablation control arm died, whereas all vaccinated patients survived. The 1-year and 2-year recurrence rates in vaccination arm compared with control arm are 18.2%, respectively. LK101 induced neoantigen-specific T cell responses were investigated by ELISpot analysis. Overall, all patients elicited at least one measurable response. Immune responses to 60-90% of neoantigen peptides were seen post vaccination across patients. Both preexisting immune response and De Novo immune response that targeted neoantigens were observed in vaccinated patients. Moreover, both CD4 and CD8 positive effector memory T cells showed the trend of increase, and PD-1 positive T cells reduced in peripheral blood of patients after vaccination. Conclusions: Combination of LK101 with ablation therapy has a manageable safety profile, showing the evidence of immune activation and potential of prolonged survival. In combination with regular ablation, neoantigen based mRNA loaded DC vaccine is a promising immunotherapy for the treatment of HCC. Clinical trial information: NCT03674073 .

Low-dose radiation as a preconditioning regimen for dendritic cell vaccines.

e14519 Background: Dendritic cells are potent antigen-presenting cells that induce the adaptive immune system to protect against cancer. While anti-tumor immunity can be improved with dendritic cell vaccines, it is not fully known what approved preconditioning agents, if any, improve dendritic cell vaccine-induced antitumor T-cell response and tumor elimination. We explored the effect of low-dose radiation (LDR), cyclophosphamide, and paclitaxel as preconditioning regiments for a dendritic cell vaccine. Methods: KP tumors were engineered with ovalbumin and orthotopically injected subcutaneously (SQ) into the flank of wild type B6 mice. Preconditioning regiments of a control, LDR (2 Gy), cyclophosphamide (20mg/kg), LDR (2 Gy) + cyclophosphamide (20mg/kg), and paclitaxel (20mg/kg) were given on day 4. Bone marrow dendritic cells (DCs) were electroporated with ovalbumin peptide SIINFEKL and then one million cells were injected i.v. on day 5 and 8. Blood collection was done and ovalbumin-specific T-cell populations were examined by tetramer staining for SIINFEKL-specific TCR over time. Tumor size was measured over time and survival data was analyzed accordingly. Results: LDR effectively produced a significant increase in CD8+ SIINFEKL tetramer+ T-cell count per uL of blood compared to the non-preconditioned group. In addition, this LDR preconditioning regiment produced a significantly improved tumor response over time. The overall survival rate of subjects receiving LDR was significantly improved compared to all other groups. Conclusions: Here, we find that LDR is most effective as a preconditioning regimen prior to dendritic cell vaccination for inducing an antitumor T-cell response and achieving tumor control over time. LDR provides a promising method to supplement dendritic cell vaccination and potentially improve patient outcomes. Further study is needed to confirm its efficacy.

A pilot trial of personalized neoantigen pulsed autologous dendritic cell vaccine as adjuvant treatment in hepatocellular carcinoma.

e16264 Background: The primary treatment for hepatocellular carcinoma (HCC) is radical surgery. However, HCC has a high propensity to recur postoperatively and no standard adjuvant therapies have been approved. This Phase I trial aims to evaluate the safety and efficacy of an adjuvant personalized neoantigen pulsed autologous dendritic cell vaccine (Neo-DCVac-02) in patients with HCC. Methods: Eligible patients had histologically confirmed high-risk HCC after radical surgery. After obtaining the necessary baseline biopsy specimens and PBMCs of appropriate quality for DNA and RNA sequencing, neoantigen prediction, screening and synthesis were performed. Subsequently, leukapheresis was performed and DCs were isolated and cultured. DCs were then pulsed with neoantigen peptides to produce Neo-DCVac-02. On day 0, patients were treated with cyclophosphamide at a dose of 250 mg/m2. The prepared Neo-DCVac-02 vaccine was administered subcutaneously to the axillary and inguinal regions bilaterally on day 1, followed by daily administration of GM-CSF at a dose of 0.075 mg for 5 days (days 2-6). The primary objectives of this study were to assess feasibility and safety/tolerability. Secondary objectives included evaluation of immune responses (via vaccine response: IFNγ ELISpot), relapse-free survival (RFS) and overall survival (OS). Results: A total of 32 patients provided informed consent to initiate the process of personalized neoantigen discovery, of which 26 (81%) met the requirements for successful product selection for clinical manufacturing. Feasibility was demonstrated with 13 patients receiving Neo-DCVac-02. 13 patients did not receive the neoantigen vaccine (7 due to progressive disease, 6 due to withdrawal of informed consent because of COVID-19). The treatment was well tolerated with no grade 2+ treatment-related adverse events (TRAEs). The most common Grade 1 TRAEs were injection site reactions (75%), rash (16.7%), fatigue (8.3%), neutropenia (8.3%), and headache (8.3%). Five of 13 evaluable patients showed increased antigen-specific T-cell activity and more than 50% of the neoantigen peptides in Neo-DCVac-02, and sustained cellular responses were observed up to one year. Increases in T-cell activation/co-stimulation seen after treatment with Neo-DCVac-02, as demonstrated by flow cytometric analysis, suggest immune priming. At a median follow-up of 29.7 months, median RFS was not reached, with 1- and 2-year RFS of 84.6% and 60%, respectively, and all patients are alive. Patients with a strong immune response had a longer median relapse-free survival (not reached) compared to patients with a weak immune response (17.6 months, P = 0.003). Conclusions: These data demonstrate that Neo-DCVac-02 is safe, well tolerated and capable of inducing durable antigen-specific lymphocyte immune responses that may correlate with delayed HCC recurrence. Clinical trial information: NCT04147078 .

Efficacy of intrathecal delivery of peptide-pulsed type 1 conventional dendritic cell vaccine for the treatment of breast cancer-associated leptomeningeal disease in preclinical models.

Efficacy of intrathecal delivery of peptide-pulsed type 1 conventional dendritic cell vaccine for the treatment of breast cancer-associated leptomeningeal disease in preclinical models.

Immunological profiling of glioblastoma cellular composition to predict response to dendritic cell vaccination.

e14037 Background: Glioblastomas are the most common primary malignant brain tumors, comprising 2% of all adult cancers. Despite recent advancements in genetic classification and targeted therapies for specific mutations, there has been no significant improvement in overall life expectancy for the majority of patients. Last year, our research group reported promising results from a phase II prospective trial involving allogeneic dendritic cell vaccination. To date, six out of 37 reported cases remain alive without tumor recurrence, exhibiting a performance status of 90 to 100% according to the Karnofsky Performance Scale (KPS) three years after the initiation of vaccination. Methods: In this study, we focused on the immune cell infiltration observed at the time of tumor excision in enrolled patients. We utilized flow cytometry to quantify cells expressing membrane CD86, CD45, HLA-DR, PD-L1, CD11b, and CD14, in addition to assessing IDH-1 status, age, gender, KPS, gender, ECOG, symptomatology, and the number of vaccines administered during the trial. Our goal was to predict responsiveness in terms of overall survival using a neural network prediction algorithm with three hidden nodes and five seeds for improved reproducibility. We employed the random holdback method for algorithm validation. Results: From the 37 enrolled patients, we successfully obtained viable tumor cells from 19 frozen samples. The model achieved an RSquare value of 0.71 after training and 0.66 after validation (where 1 indicates a perfect model and 0 implies no improvement over a constant model). Similar RSquare values in both training and validation sets indicate strong predictive power. Positive predictors of overall survival included HLA-DR positivity, PD-L1 positivity, IDH-1 mutation status, the presence of focal deficits, and higher KPS scores, while negative predictors were CD86 expression, older age, symptoms of intracranial hypertension (ICH), and higher ECOG performance status. Conclusions: In conclusion, the neural network algorithm described herein enables the prediction of responsiveness to dendritic cell vaccination in terms of overall survival, based on clinical features and the profile of immune cell infiltration observed at the time of tumor excision.

Dendritic cell vaccine as a strategy to prevent melanoma recurrence after local resection: A systematic review and meta-analysis.

e21561 Background: Melanoma has a high risk of recurrence and death even following complete surgical excision, specially in stages III and IV. Immunotherapy with checkpoint inhibitors, among other treatments, has been employed as adjuvant therapy in an effort to improve overall survival (OS) and disease free survival (DFS) in these patients. Cancer vaccines, particularly those based on dendritic cells loaded with tumor lysate particles (TLPLDC), have been investigated as new adjuvant therapy, these vaccines utilize autologous tumor lysate from an individual tumor, captured by dendritic cells to generate a personalized vaccine that stimulates an active cellular immune response. We conducted a meta-analysis to assess the effectiveness of these vaccines in patients with melanoma following complete resection. Methods: We searched in Pubmed, Cochrane and Embase in December 2023 for articles evaluating the effectiveness of TLPLDC vaccines on the recurrence and survival of patients with locoregional melanoma completely resected. The outcomes of interest included DFS for 3 years and OS for 2 and 3 years, comparing TLPLDC against the control. Additionally, we performed a subgroup analysis comparing an alternative TLPLDC technique named TLPLDC+G against the control. Random-effects models were employed to pool hazard ratios from studies using R software version 4.3.1. Results: We included 4 randomized controlled trials comprising 564 patients. The OS at the 3-year follow-up favored TLPLDC against control (logHR = -1.718[-2.697,-0.740], p = 0.0006,I² = 0%). In the 2-year comparison, treatment was also favored (logHR = -1.511,CI[-2.743,-0.279],p = 0.0162,I² = 36%). However, TLPLDC+G did not exhibit a statistically significant difference from the control in the 3-year long comparison (logHR = 0.043[-0.504,0.590],p = 0.8780,I² = 0%). Regarding the DFS in 36-month comparison, TLPLDC was favored with a 95% CI (logHR = -0.419,[-0.831,-0.006],p = 0.0468,I² = 48%). For TLPLDC+G, there was no statistical difference (0.269[-0.07,0.609],p = 0.1201,I² = 0%). Conclusions: Our results suggests that TLPLDC had a significant impact on OS at 2 and 3-year follow-up with a relatively low heterogeneity between the studies. Regarding the DFS, the TLPLDC group showed a significant difference favoring the vaccine; however, it presented higher heterogeneity. The TLPLDC+G subgroup did not exhibit a significant difference from control in both OS and DFS. Despite the favorable outcomes associated with the TLPLDC vaccine it is important to consider the potential effects of curve reconstruction, the limited number of studies, individual variations in patients immune responses, and differences in vaccine protocols between institutions as limitations of our analysis.

New Horizons and Breakthroughs in the Therapeutic Treatments for Glioblastoma

Glioblastoma represents a difficult challenge in both oncology and neurosurgery, characterized by its aggressive nature and poor prognosis. Despite its multimodal approach to standard treatment, combining surgery and chemoradiation therapy, the overall survival for patients remains disappointingly low. This review paper provides an overview of the clinical challenges associated with glioblastoma treatment, including tumor heterogeneity, low mutational burden, cancer stemness, and its immunosuppressive microenvironment. In addition, we explore promising future therapies such as the tumor treating fields (TTFields), carmustine wafer treatment, angiogenesis inhibition, CRISPR-Cas9 genome editing therapy, and immunotherapies such as dendritic cell vaccination (DCV) and immune checkpoint inhibitors (ICIs). Across the review, we highlight the potential, progress, and shortcomings of each therapeutic approach by addressing their respective success and challenges. By analyzing this information, we strive to provide a comprehensive review of the current progress of glioblastoma treatment and its future therapeutic potential.

A chemically induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development.

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca- vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.