Molecular Templates Inc. has received IND clearance from the FDA for its novel MT-8421 engineered toxin bodies (ETB) program targeting cytotoxic T-lymphocyte protein 4 (CTLA-4) in patients with relapsed/refractory solid tumors previously exposed to checkpoint inhibitors. MT-8421 is designed to eliminate CTLA-4-expressing regulatory T cells (Tregs) in the tumor microenvironment (TME) through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon while not affecting Tregs in the periphery.

A deficiency in fumarate metabolism could be behind a new mechanism of inflammation mediated by mitochondrial DNA and RNA. Two independent and simultaneous studies described how the accumulation of fumarate in the mitochondria released the genetic material of this organelle through vesicles, activating an inflammatory signaling pathway.

Estrella Biopharma Inc. has received FDA clearance of its IND application for lead product candidate EB-103, a T-cell therapy targeting CD19, a protein expressed on the surface of almost all B-cell leukemias and lymphomas.

Researchers from the Brigham and Women’s Hospital and Harvard Medical School and collaborators recently conducted a study investigating the regulation of immune checkpoint molecules in cancer. Analyzing data from The Cancer Genome Atlas pan-cancer cohort (over 10,000 patients and 11,000 samples across 34 different cancer subtypes), they found that high expression of the immune checkpoint B7-H3 (CD276) and high mTORC1 activity correlate with immunosuppressive phenotypes and worse clinical outcomes.

Whether as primary tumors or metastases, brain tumors remain stubbornly intractable to the progress that has occurred in many other tumor types. As Igor Vivanco, who is a senior lecturer in the Institute of Pharmaceutical Science at King’s College London, noted in his talk at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) meeting in Paris this week, the last win in glioblastoma was the addition of temozolomide to the radiotherapy standard of care in 2005. And temozolomide’s benefit is measured in months, not years.

In a striking demonstration of how the success of mRNA vaccines against COVID-19 has opened up the potential of the technology in cancer, mice that cleared a tumor after a single administration of an mRNA vaccine, also cleared a second tumor without receiving further immunization. This display of potent immunogenicity formed part of a head-to-head study of three different mRNA technology platforms in human papillomavirus (HPV)-16 associated tumors.