γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer.

Immune checkpoint blockade has been largely unsuccessful for the treatment of bone metastatic castrate-resistant prostate cancer (mCRPC). Here, we report a combinatorial strategy to treat mCRPC using γδ-enriched chimeric antigen receptor (CAR) T cells and zoledronate (ZOL). In a preclinical murine model of bone mCRPC, γδ CAR-T cells targeting prostate stem cell antigen (PSCA) induced a rapid and significant regression of established tumors, combined with increased survival and reduced cancer-associated bone disease. Pretreatment with ZOL, a U.S. Food and Drug Administration-approved bisphosphonate prescribed to mitigate pathological fracture in mCRPC patients, resulted in CAR-independent activation of γδ CAR-T cells, increased cytokine secretion, and enhanced antitumor efficacy. These data show that the activity of the endogenous Vγ9Vδ2 T cell receptor is preserved in CAR-T cells, allowing for dual-receptor recognition of tumor cells. Collectively, our findings support the use of γδ CAR-T cell therapy for mCRPC treatment.

γδ T Cell-Based Adoptive Cell Therapies Against Solid Epithelial Tumors.

ABSTRACT: Conventionally, adoptive cell therapies have been developed and optimized using αß T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell-based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of discussion in the field, pertaining to their use in adoptive immunotherapy. We aimed to compile information about γδ T-cell enhancement in terms of expansion, phenotype, and inhibitory receptors, in addition to the latest advances in preclinical and clinical research using γδ T cells specifically against solid epithelial tumors.

A new polytypic species of yellow-shouldered bats, genus Sturnira (Mammalia: Chiroptera: Phyllostomidae), from the Andean and coastal mountain systems of Venezuela and Colombia.

Sturnira is the most speciose genus of New World leaf-nosed bats (Phyllostomidae). We name Sturnira adrianae, new species. This taxon is born polytypic, divided into a larger subspecies (S. a. adrianae) widespread in the mountains of northern and western Venezuela, and northern Colombia, and a smaller subspecies (S. a. caripana) endemic to the mountains of northeastern Venezuela. The new species inhabits evergreen, deciduous, and cloud forests at mainly medium (1000-2000 m) elevations. It has long been confused with S. ludovici, but it is more closely related to S. oporaphilum. It can be distinguished from other species of Sturnira by genetic data, and based on discrete and continuously varying characters. Within the genus, the new species belongs to a clade that also includes S. oporaphilum, S. ludovici, S. hondurensis, and S. burtonlimi. The larger new subspecies is the largest member of this clade. The two new subspecies are the most sexually dimorphic members of this clade. The smaller new subspecies is restricted to small mountain systems undergoing severe deforestation processes, therefore can be assigned to the Vulnerable (VU) conservation category of the International Union for Conservation of Nature (IUCN).