Remodeling the tumor immune microenvironment through hydrogel encapsulated G-Rh2 vaccine and systemic immunotherapy.

Ginsenoside Rh2 (G-Rh2) is a vital bioactive compound in Traditional Chinese Medicine, celebrated for its strong pharmacological properties, particularly its potent antitumor effects. However, its poor water solubility and limited bioavailability have necessitated the development of a novel drug delivery method. In this study, we utilized an indocyanine green carboxylic acid-hydroxypropyl cellulose-abietic acid-bovine serum albumin hydrogel (ICG-HPC-AA/BSA hydrogel) as a tumor vaccine to enhance the permeability, retention, and tumor-targeted therapeutic efficacy of G-Rh2.

Efficacy of MAGE-A4 long peptide as a universal immunoprevention cancer vaccine.

Background: The clinical application of peptide vaccines in tumor immunotherapy holds significant promise. Peptide-based tumor vaccines are currently subject to certain limitations in clinical trials, including the challenge of inducing a sustained response from CD4 T helper cells and cytotoxic T lymphocytes (CTL), as well as human leukocyte antigen (HLA) restrictions.

Methods: Through the utilization of biological information methodology, a screening process was conducted to identify three potential long peptides that are specifically targeted by the MAGE-A4 antigen.

enhances shikonin-induced immunogenic cell death-an efficient tumor vaccine strategy.

Tumor vaccines are a promising avenue in cancer immunotherapy. Despite the progress in targeting specific immune epitopes, tumor cells lacking these epitopes can evade the treatment. Here, we aimed to construct an efficient tumor vaccine called Vac-SM, utilizing shikonin (SKN) to induce immunogenic cell death (ICD) and as an immune adjuvant to enhance tumor vaccine efficacy.

Development of a manganese complex hyaluronic acid hydrogel encapsulating stimuli-responsive Gambogic acid nanoparticles for targeted Intratumoral delivery.

Gambogic acid is a natural compound with anticancer properties and is effective for many tumors. But its low water solubility and dose-dependent side effects limit its clinical application. This study aims to develop a novel drug delivery system for intratumoral delivery of gambogic acid.

A Thermosensitive Bi-Adjuvant Hydrogel Triggers Epitope Spreading to Promote the Anti-Tumor Efficacy of Frameshift Neoantigens.

Tumor-specific frameshift mutations encoding peptides (FSPs) are highly immunogenic neoantigens for personalized cancer immunotherapy, while their clinical efficacy is limited by immunosuppressive tumor microenvironment (TME) and self-tolerance. Here, a thermosensitive hydrogel (FSP-RZ-BPH) delivering dual adjuvants R848 (TLR7/8 agonist) + Zn (cGAS-STING agonist) is designed to promote the efficacy of FSPs on murine forestomach cancer (MFC). After peritumoral injection, FSP-RZ-BPH behaves as pH-responsive sustained drug release at sites near the tumor to effectively transform the immunosuppressive TME into an inflammatory type.

Bivalent Gadolinium Ions Forming Injectable Hydrogels for Simultaneous In Situ Vaccination Therapy and Imaging of Soft Tissue Sarcoma.

Doxorubicin (DOX) is the classic soft tissue sarcomas (STS) first-line treatment drug, while dose-dependent myelosuppression and cardiotoxicity limit its application in clinic. This research intends to apply DOX, which is also an inducer of immunogenic cell death as a part for "in situ vaccination" and conjointly uses PD-1 inhibitors to enhance antitumor efficacy. In order to achieve the sustained vaccination effect and real-time monitoring of distribution in vivo, the in situ forming and injectable hydrogel platform with the function of visualization is established for local delivery.

Engineering a HemoMap Nanovaccine for Inducing Immune Responses against Melanoma.

Neoantigen vaccines have opened a new paradigm for cancer immunotherapy. Here, we constructed a neoantigen nanovaccine-HemoMap, with the ability to target lymph nodes and activate immune cells. We propose a HemoMap nanovaccine consisting of the mouse melanoma highly expressed antigenic peptide Tyrp1 and a magnesium nanoadjuvant-HemoM.

Benefits of an Immunogenic Personalized Neoantigen Nanovaccine in Patients with High-Risk Gastric/Gastroesophageal Junction Cancer.

Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumor immune response. Here, a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy is generated. PNVAC triggers superior protective efficacy against tumor recurrence and promotes longer survival than free neoantigens, especially when combined with anti-PD-1 treatment in a murine tumor model.

A dual-adjuvant neoantigen nanovaccine loaded with imiquimod and magnesium enhances anti-tumor immune responses of melanoma.

Neoantigen-based tumor vaccines have been applied in patient-specific melanoma-derived immunogenic mutated epitopes (neoantigens), with potential antineoplastic and immunomodulating effects. Yet, their use is limited by different physicochemical properties and poor pharmacokinetics. Herein, we constructed a human serum albumin-based dual adjuvant neoantigen nanovaccine loaded with imiquimod and magnesium.

Combination of Peglated-H1/HGFK1 Nanoparticles and TAE in the Treatment of Hepatocellular Carcinoma.

Transarterial embolization (TAE) constitutes the gold standard for the treatment of hepatocellular carcinoma. The effect of combination of TAE and peglated-H1/HGFK1 nanoparticles was explored on hepatocellular carcinoma. MTT and Annexin V-FITC were used to determine the cell viability and apoptosis of HepG2, ml-1, LO2, and VX2 cells after the treatment of HGFK1.

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report.

Personal neoantigen vaccines are considered to be effective methods for inducing, amplifying and diversifying antitumor T cell responses. We recently conducted a clinical study that combined neoantigen nanovaccine with anti-PD-1 antibody. Here, we reported a case with a clear beneficial outcome from this treatment.

Case Report: Pathological Complete Response in a Lung Metastasis of Phyllodes Tumor Patient Following Treatment Containing Peptide Neoantigen Nano-Vaccine.

Some of the mutant peptides produced by gene mutation transcription and translation have the ability to induce specific T cells, which are called new antigens. Neoantigen-based peptide, DNA, RNA, and dendritic cell vaccines have been used in the clinic. In this paper, we describe a lung metastasis of a phyllodes tumor patient demonstrating pathological complete response following treatment containing personalized multi-epitope peptide neoantigen nano-vaccine.

A Simple and Efficient Synthesis of Highly Substituted Indeno[1,2-]pyrrole and Acenaphtho[1,2-]pyrrole Derivatives by Tandem Three-Component Reactions.

A green, convenient and tandem procedure for the efficient synthesis of highly substituted indeno[1,2-]pyrrole and acenaphtho[1,2-]pyrrole derivatives by domino three-component reaction of tryptamine/benzylamine, 1,3-dicarbonyl compounds and ninhydrin/ acenaphthenequinone is described. The significant features of this procedure were characterized by mild reaction conditions, high yields, operational simplicity and it being environmentally benign.

Oral administration of indole substituted dipyrido[2,3-d]pyrimidine derivative exhibits anti-tumor activity via inhibiting AKT and ERK1/2 on hepatocellular carcinoma.

Development of an effective and safe anti-cancer drug is an urgent request for hepatocellular carcinoma (HCC). In this study, we synthesized a series of novel indole substituted dihydropyrido[2,3-d]pyrimidines through the multicomponent reactions to connect pyrido[2,3-d]pyrimidine and indole moities via an one-pot three-component reaction of 3-cyanoacetyl indoles 1, various aromatic aldehyde 2, and 2,6-diaminopyrimidin-4(3H)-one 3. Subsequently, we screened their cytotoxicity via CCK-8 assay in HepG2 cells, a human hepatoma cell line and chose compound 4p that showed the lowest dosage of IC50 to study the antitumor activities to HCC.

A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma.

Successful immunogene therapy depends not only on the therapeutic gene but also on the gene delivery vector. In this study, we synthesized a novel copolymer consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo-inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI. We characterized the chemical structure and molecular weight of the copolymer and particle properties of LA-PegPI/pDNA.