Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated Cancers: A Nonrandomized Clinical Trial.

Importance: Patients who experience progression of advanced human papillomavirus (HPV)-associated cancers and who have previously received first-line systemic treatment have a poor prognosis and limited therapeutic options.

Objective: To assess the clinical activity of the combination of the HPV type 16 therapeutic vaccine PDS0101, the tumor-targeting interleukin 12 antibody-drug conjugate PDS01ADC, and the bifunctional anti-programmed cell death ligand 1 (PD-L1)/transforming growth factor β (TGF-β) bintrafusp alfa in advanced HPV-associated cancers.

Design, Setting, And Participants: This nonrandomized clinical trial was phase 1/2 and investigator initiated, and was conducted at a single US cancer research center between June 2020 and July 2022.

TGF-β neutralization attenuates tumor residency of activated T cells to enhance systemic immunity in mice.

A tissue resident-like phenotype in tumor infiltrating T cells can limit systemic anti-tumor immunity. Enhanced systemic anti-tumor immunity is observed in head and neck cancer patients after neoadjuvant PD-L1 immune checkpoint blockade (ICB) and transforming growth factor β (TGF-β) neutralization. Using T cell receptor (TCR) sequencing and functional immunity assays in a syngeneic model of oral cancer, we dissect the relative contribution of these treatments to enhanced systemic immunity.

A deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an indirect two-step approach consisting of (1) DeepPT, a deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response to targeted and immune therapies from the inferred expression values. We show that DeepPT successfully predicts transcriptomics in all 16 The Cancer Genome Atlas cohorts tested and generalizes well to two independent datasets.

Crystal structures of sulfonamide protected bicyclic guanidines: ()-8-{[(-butyl-dimethyl-sil-yl)-oxy]meth-yl}-1-[(2,2,4,6,7-penta-methyl-2,3-di-hydro-benzo-furan-5-yl)sulfon-yl]-1,3,4,6,7,8-hexa-hydro-2-pyrimido[1,2-]pyrimidin-1-ium tri-fluoro-methane-sulfonate and ()-8-(iodo-meth-yl)-1-tosyl-1,3,4,6,7,8-hexa-hydro-2-pyrimido[1,2-]pyrimidin-1-ium iodide.

Two compounds, ()-8-{[(-butyl-dimethyl-sil-yl)-oxy]meth-yl}-1-[(2,2,4,6,7-penta-methyl-2,3-di-hydro-benzo-furan-5-yl)sulfon-yl]-1,3,4,6,7,8-hexa-hydro-2-pyrimido[1,2-]pyrimidin-1-ium tri-fluoro-methane-sulfonate, CHNOSSi·CFOS, () and ()-8-(iodo-meth-yl)-1-tosyl-1,3,4,6,7,8-hexa-hydro-2-pyrimido[1,2-]pyrimidin-1-ium iodide, CHINOS·I, (), have been synthesized and characterized. They are bicyclic guanidinium salts and were synthesized from -(-but-oxy-carbon-yl)-l-me-thio-nine (Boc-l-Met-OH). The guanidine is protected by a 2,2,4,6,7-penta-methyl-dihydro-benzo-furan-5-sulfonyl (Pbf, ) or a tosyl () group.