ORCID Profile
0000-0002-7006-4339
Current Organisations
University of Wisconsin–Madison
,
Zhejiang University of Technology
,
Hangzhou Neoantigen Therapeutics Co., Ltd
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Publisher: Frontiers Media SA
Date: 13-08-2021
DOI: 10.3389/FIMMU.2021.691605
Abstract: Neoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients. This retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood s les of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry. No severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4 + or CD8 + effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells. Neoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer. ClinicalTrials.gov , identifier (NCT03645148). Registered August 24, 2018 - Retrospectively registered
Publisher: MDPI AG
Date: 11-06-2021
DOI: 10.3390/PATHOGENS10060737
Abstract: Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-γ-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-γ-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required.
Publisher: MDPI AG
Date: 28-05-2021
Abstract: The production of subunit nanovaccines relies heavily on the development of a vaccine delivery system that is safe and efficient at delivering antigens to the target site. Nanoparticles have been extensively investigated for vaccine delivery over the years, as they often possess self-adjuvanting properties. The conjugation of antigens to nanoparticles by covalent bonds ensures co-delivery of these components to the same subset of immune cells in order to trigger the desired immune responses. Herein, we review covalent conjugation strategies for grafting protein or peptide antigens onto other molecules or nanoparticles to obtain subunit nanovaccines. We also discuss the advantages of chemical conjugation in developing these vaccines.
Publisher: Wiley
Date: 08-01-2023
Abstract: Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE‐J8 (PJ8), derived from Group A Streptococcus (GAS) M‐protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod‐shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)‐adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 06-2022
DOI: 10.1200/JCO.2022.40.16_SUPPL.3151
Abstract: 3151 Background: We previously reported the safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, in patients with a variety of cancer types. The current study investigated the synergistic effects between radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice. Methods: 28 cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before scheduled for vaccination, and 18 patients who had not. In idualized neoantigen peptide vaccines were designed, manufactured, and delivered for all patients, followed by subcutaneous administration of GM-CSF as an adjuvant. Mouse models were used to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination. Results: Longer median progression free survival (mPFS) and median overall survival (mOS) were observed in patients receiving RFA prior to vaccines compared to patients only receiving vaccines (4.42 and 20.18 months vs. 2.82 and 10.94 months). Ex vivo ELISpot assay showed that patients who received both had stronger IFN-γ responses against patient-specific neoantigens at baseline and post vaccination. Mice receiving RFA together with vaccine displayed higher antitumor immune responses than mice receiving single modality addition of anti-PD-1 further enhanced the antitumor response. Conclusions: Neoantigen vaccination after RFA treatment led to an overall increase in clinical response and immune response among patients of different cancer types. Combination treatment of both modalities in mice further validated their synergistic antitumor potentials, which could be further enhanced by the addition of anti-PD-1. The mechanisms of their synergies require further investigation. Clinical trial information: NCT03662815.
Publisher: Frontiers Media SA
Date: 29-09-2022
DOI: 10.3389/FIMMU.2022.1000681
Abstract: The safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, was reported previously in patients with a variety of cancer types. The current study investigated the synergistic effects of radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice. Twenty-eight cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before vaccination (Cohort 1), and 18 patients who had not (Cohort 2). In idualized neoantigen peptide vaccines were designed, manufactured, and subcutaneously administrated with GM-CSF as an adjuvant for all patients. Mouse models were employed to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination. Longer median progression free survival (mPFS) and median overall survival (mOS) were observed in patients in Cohort 1 compared to patients in Cohort 2 (4.42 and 20.18 months vs. 2.82 and 10.94 months). The results of ex vivo IFN-γ ELISpot assay showed that patients in Cohort 1 had stronger neoantigen-specific immune responses at baseline and post vaccination. Mice receiving combination treatment of RFA and neoantigen vaccines displayed higher antitumor immune responses than mice receiving single modality. The combination of PD-1 blockage with RFA and neoantigen vaccines further enhanced the antitumor response in mice. Neoantigen vaccination after local RFA treatment could improve the clinical and immune response among patients of different cancer types. The synergistic antitumor potentials of these two modalities were also validated in mice, and might be further enhanced by immune checkpoint inhibition. The mechanisms of their synergies require further investigation. clinicaltrials.gov/ , identifier NCT03662815.
Publisher: MDPI AG
Date: 10-02-2023
DOI: 10.3390/PHARMACEUTICS15020602
Abstract: Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.
No related grants have been discovered for Lantian Lu.