Comprehensive approach to cancer immunotherapy - Simultaneous targeting of myeloid-derived suppressor cells and cancer cells with AFP conjugates.

The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article describes a novel strategy for cancer treatment centered on depleting myeloid-derived suppressor cells (MDSCs), to enhance the overall immune response while simultaneously targeting cancer cells directly. Alpha-fetoprotein (AFP) is an oncofetal protein that plays an important role in delivering nutrients to immature monocytes, embryonic, and cancer cells in a targeted manner.

The use of alpha-fetoprotein for the treatment of autoimmune diseases and cancer.

Alpha-fetoprotein is a shuttle protein that delivers nutrients through receptor-mediated endocytosis to embryotic cells. In adults, alpha-fetoprotein can shuttle drugs into alpha-fetoprotein receptor-positive myeloid-derived suppressor, regenerating and also cancer cells. Drugs with high-binding affinity to alpha-fetoprotein can activate or deplete targeted cells.

TGF-β triggers HBV cccDNA degradation through AID-dependent deamination.

The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a viral center molecule for HBV infection and persistence. However, the cellular restriction factors of HBV cccDNA are not well understood. Here, we show that TGF-β can induce nuclear viral cccDNA degradation and hypermutation via activation-induced cytidine deaminase (AID) deamination activity in hepatocytes.

CDK11 in TREX/THOC Regulates HIV mRNA 3' End Processing.

Transcriptional cyclin-dependent kinases play important roles in eukaryotic gene expression. CDK7, CDK9 (P-TEFb), and CDK13 are also critical for HIV replication. However, the function of CDK11 remained enigmatic.

The use of α-fetoprotein for the delivery of cytotoxic payloads to cancer cells.

One approach to improving the activity of anticancer drugs is to bind them to the human α-fetoprotein (HAFP) that recognizes the tumor-associated cell-surface HAFP receptor. A drug can be bound to the HAFP by covalent conjugation or within a non-covalent complex. Specially designed linkers couple cytotoxins to the HAFP and ensure the stability of the HAFP-drug conjugate in the circulation and the activation of the drug in the cancer cell.

The role of amino-terminal sequences in cellular localization and antiviral activity of APOBEC3B.

Human APOBEC3B (A3B) has been described as a potent inhibitor of retroviral infection and retrotransposition. However, we found that the predominantly nuclear A3B only weakly restricted infection by HIV-1, HIV-1Δvif, and human T-cell leukemia virus type 1 (HTLV-1), while significantly inhibiting LINE-1 retrotransposition. The chimeric construct A3G/B, in which the first 60 amino acids of A3B were replaced with those of A3G, restricted HIV-1, HIV-1Δvif, and HTLV-1 infection, as well as LINE-1 retrotransposition.

Neutrophil activity in chronic granulomatous disease.

The killing of microorganisms by neutrophils causes degranulation of azurophilic, specific, and gelatinase granules into the formed phagolysosomes. During the degranulation process, increased surface expression of CD63 (localized in the azurophilic granules of resting neutrophils) and CD66b/CD67 (from specific granules) can be detected. This results from the fusion of the granule membrane, containing these markers, with a plasma membrane.