Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
Published: December 2024
AI Article Synopsis
Article Abstract
Safely and effectively harnessing innate immunity to boost cancer immunotherapy is promising yet challenging. Hence, we have developed a series of programmable aptamer-based multispecific engagers by encoding various artificial aptamer-drug codons with DNA-templated polymerization, aiming to broadly boost innate and adaptive immunity for antitumor therapy. All circular single-stranded multivalent aptamer-drug conjugates (os-mvApDCs) had a dendritic structure, precise size, and excellent stability, enabling prolonged blood circulation, targeted tumor accumulation, and rapid multireceptor-mediated endocytosis. A trispecific engager (os-mvApDCs), targeting PD-1 on CD8 T cells and PD-L1/c-Met on tumor cells, recruited large amounts of immune cells into the tumor and released cytotoxic MMAE and immunomodulators, inducing severe cell death and broad activation of innate immunity. When combined with the αPD-1 blockade, there was a significant increase in the number of CD8 T cells (10-fold increase versus untreated control) engaged and expanded in the tumor, exhibiting potent function (IFN-γ/GzmB) and low exhaustion (PD-1TIM-3). The orchestrated innate and adaptive immunity effectively eliminated immunosuppressive MDSCs, Tregs, and M2-like macrophages in tumors and promoted the maturation of dendritic cells (DCs) in the draining lymph nodes, resulting in robust and durable systemic antitumor efficacy, with 7 out of 8 mice surviving over 60 days. Our programmable DNA-templated printing technology enables the rational design of multispecific therapeutics with modular composition and function but minimal production issues, providing a versatile tool for the development of multifunctional personalized medicine.
Magnetic field regulation is an effective strategy to improve the photocatalytic activity of magnetic semiconductor photocatalysts, but it is not suitable for widely used nonmagnetic photocatalytic semiconductors. Here, we report a Zeeman effect-driven spin-polarized band splitting phenomenon in diluted magnetic semiconductors that show efficient photocatalytic CO reduction under visible-light irradiation. A flexible Ni-doped BaTiO nanofiber film is used as the diluted magnetic semiconductor model to prove this concept.
Viral products keep gaining importance in multiple therapeutic fields. Considering the scale and production slot limitations, optimizing the outcome of every manufacturing batch is essential to minimize costs and make this therapeutic modality broadly available to patients. Most manufacturing processes for oncolytic viruses currently in clinical studies are based on a batch process.
Introduction: Coronaviruses and influenza viruses are significant respiratory pathogens that cause severe disease burdens and economic losses for society. Due to their diversity and evolution, vaccines typically require periodic updating to remain effective. An additional challenge is imposed by the possible coinfection of SARS-CoV-2 and influenza, which could increase disease severity.
Rare B cells can have special pathogen-recognition features giving them the potential to make outsized contributions to protective immunity. However, rare naive B cells infrequently participate in immune responses. We investigated how germline-targeting vaccine antigen delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (~1 in 50 million) in non-human primates.
Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure.
