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The BCL-2 prosurvival protein is implicated in HIV persistence and is a potential therapeutic target for HIV eradication efforts. We now know that cells harboring HIV are preferentially enriched for high BCL-2 expression, enabling their survival, and that the BCL-2 inhibitor venetoclax promotes the death of actively replicating HIV-infected cells in vitro and ex vivo. Herein, we assess the effect of venetoclax on immune clearance of infected cells and show that BCL-2 inhibition significantly enhances target cell killing induced by Fas ligand, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and perforin/granzyme B and synergistically enhances autologous NK (natural killer) and CD8 cells’ killing of target cells. I

The hostile tumor microenvironment (TME) is a major challenge for the treatment of solid tumors with T-cell receptor (TCR)-modified T-cells (TCR-Ts), as it negatively influences T-cell efficacy, fitness, and persistence. These negative influences are caused, among others, by the inhibitory checkpoint PD-1/PD-L1 axis. The Preferentially Expressed Antigen in Melanoma (PRAME) is a highly relevant cancer/testis antigen for TCR-T immunotherapy due to broad expression in multiple solid cancer indications.

Long-acting antiretrovirals could provide a useful alternative to daily oral therapy for HIV-1-infected individuals. Building on a bi-specific molecule with adnectins targeting CD4 and gp41, a potential long-acting biologic, GSK3732394, was developed with three independent and synergistic modes of HIV entry inhibition that potentially could be self-administered as a long-acting subcutaneous injection.

People living with HIV (PLWH) have expressed concern about the life-long burden and stigma associated with taking pills daily and can experience medication fatigue that might lead to suboptimal treatment adherence and the emergence of drug-resistant viral variants, thereby limiting future treatment options1-3. As such, there is strong interest in long-acting antiretroviral (ARV) agents that can be administered less frequently4.

Chronic myeloid leukemia (CML) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion transcript. Tyrosine kinase inhibitors (TKI) have significantly increased survival of patients with CML, and deep responders may consider stopping the treatment. However, more than 50% of patients relapse and restart TKI, subsequently suffering unknown toxicity.