Screening and identifying a novel M-MDSCs-related gene signature for predicting prognostic risk and immunotherapeutic responses in patients with lung adenocarcinoma.

Lung adenocarcinoma (LUAD) shows intratumoral heterogeneity, a highly complex phenomenon that known to be a challenge during cancer therapy. Considering the key role of monocytic myeloid-derived suppressor cells (M-MDSCs) in the tumor microenvironment (TME), we aimed to build a prognostic risk model using M-MDSCs-related genes. M-MDSCs-related genes were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.

Vaccine targeting TNF epitope 1-14 do not suppress host defense against Mycobacterium bovis Bacillus Calmette-Guérin infection.

Anti-TNF inhibitors are efficacious in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). However, more and more clinical case reports revealed that anti-TNF inhibitors could increase the risk of viral, fungal, and bacterial (especially intracellular) infection. In this study, based on Immune Epitope Database (IEDB) online B cell epitope prediction and the knowledge of TNF three dimensional (3D) structure we developed a novel vaccine (DTNF114-TNF114) that targeting TNF epitope 1-14, which produced antibodies only partially binding to trans-membrane TNF (tmTNF), therefore partially sparing tmTNF-TNFR1/2 interaction.

Recombinant KRAS G12D Protein Vaccines Elicit Significant Anti-Tumor Effects in Mouse CT26 Tumor Models.

Drug development targeting the most frequently mutation G12D of KRAS has great significance. As an attractive immunotherapy, cancer vaccines can overcome binding difficulties of small molecules; however, the weak immunogenicity and production difficulties of reported KRAS mutation vaccines limit their clinical application. To improve antigen-specific immune responses and Anti-Tumor effects on tumors expressing KRAS G12D mutation, we designed recombinant proteins containing KRAS peptide (amino acids 5-21) with G12D (called SP) in two forms: DTT-SP and DTSP.

Recombinant Costimulatory Fusion Proteins as Functional Immunomodulators Enhance Antitumor Activity in Murine B16F10 Melanoma.

Blocking inhibitory signaling and engaging stimulatory signaling have emerged as important therapeutic modalities for cancer immunotherapy. This study aimed to investigate immunomodulatory features of three recombinant costimulatory ligand proteins in a mouse model, which are extracellular domains of OX40-ligand (OX40L), 4-1BB-ligand (4-1BBL), or two domains in tandem, fused with the transmembrane domain of diphtheria toxin (DTT), named DTT-COS1, DTT-COS2, and DTT-COS12, respectively. In vitro study showed that DTT-COS1 and DTT-COS12 had immunological activity increasing the ratio of CD8/CD4 T cells.

The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma.

Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20-30% of neoantigens predicted to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4. Therefore, it warrants further exploration to enhance neoantigen-specific CD8 T cells responses.

A PD-L1-Based Cancer Vaccine Elicits Antitumor Immunity in a Mouse Melanoma Model.

Engagement of programmed death 1 receptor (PD-1) and its ligand PD-L1/2 induces a signal transduction pathway that inhibits the activity of tumor-infiltrating cytotoxic T lymphocytes and promotes tumor growth and metastasis. Antibodies blocking PD-1 or PD-L1 can restore antitumor T cell responses and cause long-term remission in a subset of cancer patients with advanced or refractory tumors. In this study, we asked whether PD-L1 vaccination could confer tumor control in mouse tumor models.