The discovery of novel auristatin-derived antibody drug conjugates (ADCs) with attenuated bystander activity is an area of intense research. Recently, drug-linker SGD-9501-TFA emerged as a promising c...

Abstract. Antibody-Drug Conjugates (ADCs) are poised to embed themselves as pillars of cancer therapy after decades of development and fine-tuning. The vast majority of those in preclinical and clinic...

Tubulis is innovating on the linker, payload and drug-to-antibody ratio of antibody-drug conjugates, with a modular platform that optimizes for ADC stabili...

This manuscript reports the identification of hydrophobic interaction chromatography (HIC)-shifting, nontoxic linker-payload surrogates as tool molecules for the optimization of maleimide/cysteine conjugations relevant to antibody–drug conjugates (ADCs). These linker/payload (LP) mimics allow conjugation measurement via HIC with mAbs (monoclonal antibodies) bearing engineered or interchain cysteines as conjugation sites. Importantly, the tool molecules are employed to optimize maleimide/cysteine conjugations via modern methods of process development, including high-throughput experimentation and continuous flow. Overall, our studies provide confidence that commercially available, nontoxic LP mimics can be employed successfully to optimize ADC-type conjugations in batch and flow while minimizing materials needs and experimental work in specialized facilities required for potent compound handling.

Antibody–drug conjugates (ADCs) are cancer chemotherapeutics that utilize a monoclonal antibody (mAb)-based delivery system, a cytotoxic payload, and a chemical linker. ADC payloads must be strategica...

YouTube video by Dr. Rob Swanda

A DEVD Linker Enables Dual Intracellular and Extracellular Payload Release, Sustaining Bystander Killing in Heterogeneous Tumors Even After Antigen-Positive Cell Depletion.

Snapped is a Linux box hosting a static site behind nginx, with an Nginx UI admin panel. I’ll exploit CVE-2026-27944 to decrypt a backup download from the Nginx UI to find bcrypt password hashes in a SQLite database. I’ll crack one to get SSH access. To escalate to root, I’ll exploit CVE-2026-3888, a recent vulnerability in snapd where systemd-tmpfiles deletes snap-confine’s private temp directory, allowing me to win a race condition and replace the dynamic linker with a malicious payload that runs as root.

Research on patients with advanced esophageal squamous cell carcinoma (ESCC) who have progressed on immunotherapy remains limited. BL-B01D1 is a first-in-class antibody–drug conjugate consisting of an EGFR–HER3 bispecific antibody bound to a topoisomerase I inhibitor (Ed-04) payload via a cleavable linker. Here, we present safety and efficacy data from a phase 1 study of BL-B01D1, in 82 patients previously treated for ESCC. The primary endpoint was the recommended phase 2 dose. Administered doses were 2.0 (n = 22) and 2.5 (n = 60) mg kg−1 D1D8 infusion every 3 weeks (Q3W). The confirmed objective response rate (cORR) was 29.3% (24 of 82) in all patients and 32.9% (24 of 73) among evaluable patients. For patients dosed at 2.5 mg kg−1, cORR was 39.6% (21 of 53) and disease control rate was 79.2% (42 of 53). In the 2.0 mg kg−1 group, cORR was 15.0% (3 of 20), and the disease control rate was 50.0% (10 of 20). The phase 2 dose was established at 2.5 mg kg−1 D1D8 Q3W. The incidence of G3 tr

ABSTRACT Free monomethyl auristatin E (MMAE) released from trastuzumab–valine-citrulline–p-aminobenzyl carbamate (VC-PABC)–MMAE conjugates was quantified by liquid chromatography–tandem mass spectrometry (LC–MS/MS) after incubation in rat plasma at 37°C for 4 days. A wild-type conjugate prepared by maleimide–thiol interchain cysteine conjugation showed 4% ± 3.5% release (n = 3 for each), whereas a Lys188-selective comparator prepared by click chemistry after lipoic acid ligase A–mediated modification showed 4% ± 3.5% release. To examine whether this difference could be explained by linker-payload exposure, molecular dynamics simulations were performed, and solvent-accessible surface areas (SASA) were calculated for representative wild-type interchain cysteine environments and for the Lys188 conjugate. Mean SASA values for the wild-type models were 1132–1293 Å2, all lower than that of the Lys188 model (1524 Å2). Thus, the more stable comparator exhibited the highest modeled exposure. This mismatch between modeled exposure and observed release argues against a simple exposure-driven cleavage mechanism as the primary explanation for the wild-type behavior. Instead, the results suggest that the observed payload release is influenced by bond chemistry in addition to linker exposure.