Bi-functional recombinant hybrid anti-PD-L1-IgGA antibody combines the effector functions of IgG and IgA and is also directed against the ligand of the programmed cell death1 receptor (PD-L1) to enhance cancer immunotherapy. Blocking the PD-1/PD-L1 signaling pathway using anti-PD-L1-IgGA is an effective new therapeutic approach that restores the functions of immune cells to kill cancer with high efficacy. In this study, the developed novel functional and high affinity human recombinant cross-isotype IgGA antibodies to PD-L1 were successfully produced in mammalian expression systems. We demonstrated that anti-PD-L1-IgGA has high specific binding activity to PD-L1 protein. FPIA analysis yielded a Kd of approximately 1.14 nM PD-1/PD-L1 blockade for determining the inhibition activity of anti-PD-L1 antibody was shown by TR-FRET-based blockade assay. Cross-isotype anti-PD-L1-IgGA antibodies may provide a basis for further development in cancer immunotherapy.
Signal Regulatory Protein Alpha (SIRPα) and CD163 are associated with prognosis in esophageal cancer, but their prognostic value in blood is unknown. We retrospectively analyzed a randomized controlled trial of patients undergoing surgery for esophageal cancer. Soluble SIRPα (sSIRPα) and CD163 (sCD163) were measured using enzyme-linked immunosorbent assays in serum collected on the day of surgery and postoperative day 30. Patients were followed for one year. 68 patients were included. In patients undergoing upfront surgery (n = 15), high sSIRPα predicted increased 1-year mortality and sSIRPα <23.35 μg/L identified a low-risk subgroup (N = 7/15, 46.7%) with 100% 1-year survival. In contrast, among patients receiving neoadjuvant chemotherapy (CROSS or FLOT, n = 53), low sSIRPα predicted increased 1-year mortality and sSIRPα >26.15 μg/L identified a low-risk subgroup (N = 31/53, 58.5%) with 100% 1-year survival. There was no prognostic value in sCD163. In conclusion, neoadjuvant treatment may influence the prognostic value of sSIRPα in esophageal cancer.
Invariant natural killer T cells are uniquely positioned at the interface of innate and adaptive immunity, combining CD1d-restricted antigen recognition with rapid, diverse cytokine responses and relatively low HLA-driven alloreactivity. These properties make them attractive candidates for adoptive cellular immunotherapy, yet clinical translation has remained limited by inconsistent potency and persistence. This review considers ex vivo expansion as a determinant of product state rather than a passive scale-up step. Cytokine support, antigen and co-stimulatory signals, restimulation schedule, and culture duration can alter iNKT cell subset composition, survival, phenotype, and effector function, thereby influencing therapeutic fitness. We further discuss how human iNKT cell developmental biology and subset heterogeneity provide a framework for interpreting donor variability and culture-induced drift. We also compare peripheral-blood, hematopoietic stem/progenitor cell (HSPC)-derived, and induced pluripotent stem cell (iPSC)-derived manufacturing platforms and propose critical quality attributes (CQAs) for identity, potency, persistence, survival, and manufacturing safety. Progress will require manufacturing strategies that achieve clinically relevant expansion while preserving a defined and functionally validated cell state.
