Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial.

Background: Patients with large B-cell lymphoma (LBCL) primary refractory to or relapsed within 12 months of first-line therapy are at high risk for poor outcomes with current standard of care, platinum-based salvage immunochemotherapy and autologous haematopoietic stem cell transplantation (HSCT). Lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has previously demonstrated efficacy and manageable safety in third-line or later LBCL. In this Article, we report a prespecified interim analysis of liso-cel versus standard of care as second-line treatment for primary refractory or early relapsed (within 12 months after response to initial therapy) LBCL.

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma.

The autologous anti-CD19 chimeric antigen receptor (CAR) T-cell product, lisocabtagene maraleucel (liso-cel), is administered at equal target doses of CD8 and CD4 CAR T cells. This analysis assessed safety and efficacy of liso-cel in Japanese patients with relapsed or refractory (R/R) aggressive large B-cell lymphoma (LBCL) in Cohort 3 of TRANSCEND WORLD (NCT03484702). Liso-cel (100 × 10 total CAR T cells) was administered 2-7 days after lymphodepletion.

Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors.

Indoleamine 2,3-dioxygenase (IDO1) catalyzes the first step in tryptophan breakdown along the kynurenine pathway. Therapeutic inhibition of IDO1 is receiving much attention due to its proposed role in the pathogenesis of several diseases including cancer, hypotension and neurodegenerative disorders. A related enzyme, IDO2 has recently been described.

Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target.

Trop2 is a cell-surface glycoprotein reported to be overexpressed in various types of adenocarcinomas with minimal expression in normal tissues. Recent findings that Trop2 expression correlates with tumor aggressiveness have increased interest in Trop2 as a potential target for cancer immunotherapy. The goal of this study was to extensively evaluate Trop2 expression at the transcript and protein levels in normal and tumor tissues.

Specific stimulation of MHC-transgenic mouse T-cell hybridomas with xenogeneic APC.

From the recombinant human leukocyte antigen (HLA)-DR1/H2-E(k) major histocompatibility complex (MHC) class II-transgenic mice, we have generated two CD4(+) T-cell hybridomas specific for peptides which were derived from human prostatic acid phosphatase (PAP) complexed to the human class II molecule HLA-DR1. Both hybridomas strongly react to PAP-pulsed antigen-presenting cells (APC) from transgenic mice. Interestingly, these hybridomas also responded to PAP antigen presented by HLA-DR1-positive human APC.

Antitumor vaccination with HER-2-derived recombinant antigens.

Certain types of malignant tumors overexpress HER-2, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective HER-2 vaccine for the selective immunotherapy of these malignancies, we have genetically engineered fusion proteins containing portions of extra- and intracellular HER-2 domains. Activated dendritic cells (DC) cocultured with these novel antigens (Ag) could induce potent responses of Ag-specific T-cell lines in vitro and a protection against HER-2-expressing tumor in vivo.