Theralizumab

CD28 superagonists (CD28SAs) are potent T‐cell‐activating monoclonal antibodies (mAbs). In contrast to their benign behavior and marked therapeutic efficacy as activators of regulatory T (Treg) cells in preclinical rodent models, a phase I trial of the human CD28SA TGN1412 (now called TAB08) in 2006 resulted in a life‐threatening cytokine release syndrome (CRS). We studied TAB08‐mediated Treg‐cell activation in a recently developed in vitro system of human PBMCs, which also reproduces the CRS experienced by the healthy volunteers. We show that just as in rodents, CD28SAs are potent activators and expanders of Treg cells from healthy donors and rheumatoid arthritis patients, even under effective blockade of pro‐inflammatory cytokine release by a corticosteroid. Moreover, CD28SA titration identifies a dose range where pro‐inflammatory cytokine secretion from conventional T cells is absent while appreciable Treg‐cell activation is maintained. Finally, we report that low‐dose application of TAB08 to healthy volunteers results in dose‐dependent systemic release of the Treg‐cell signature cytokine IL‐10 in the absence of the pro‐inflammatory factors associated with the CRS of the 2006 TGN1412 study. These results demonstrate the potential of appropriately dosed CD28SA and corticosteroid comedication to mobilize human Treg cells for the treatment of autoimmune and inflammatory conditions.

Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy.

A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up.

We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.