Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

Effect of framework and complementarity determining region H1 charge on the human VH-B1a domain expression, folding, stability, and solubility.

Many difficulties related to using antibodies in diagnostic and therapeutic applications can sometimes be circumvented by using smaller, less complex single domain antibodies based on variable heavy chain (VH) domain constructs such as camelid VHH domains. However, VH domains have their own limitations, including an increased tendency to aggregate. VH domains often contain hydrophobic residues within their complementarity-determining regions (CDRs) that facilitate binding to target antigens but can also mediate VH domain aggregation, which is a concern for therapeutic applications since this can trigger immune responses.

Antibody-targeted T cells and natural killer cells for cancer immunotherapy.

Background: Adoptive cell cancer therapies aim to re-engineer a patient's immune cells to mount an anti-cancer response. Chimeric antigen receptor T and natural killer cells have been engineered and proved successful in treating some cancers; however, the genetic methods for engineering are laborious, expensive, and inefficient and can cause severe toxicities when they over-proliferate.

Results: We examined whether the cell-killing capacity of activated T and NK cells could be targeted to cancer cells by anchoring antibodies to their cell surface.

Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG.

COVID-19, the disease caused by SARS-CoV-2, particularly causes severe inflammatory disease in elderly, obese, and male patients. Since both aging and obesity are associated with decreased testosterone and estradiol expression, we hypothesized that decreased hormone levels contribute to excessive inflammation in the context of COVID-19. Previously, we and others have shown that hyperinflammation in severe COVID-19 patients is induced by the production of pathogenic anti-spike IgG antibodies that activate alveolar macrophages.

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.