iNKT cells + PD-1+CD8+ T cells

This is an investigational adoptive cell therapy that combines autologous invariant natural killer T (iNKT) cells with programmed death 1-positive (PD-1+) CD8+ T cells. The approach involves isolating both iNKT and PD-1-expressing CD8+ cytotoxic T lymphocytes from the patient, expanding them ex vivo, and then infusing them back into the patient. iNKT cells are a unique subset of lymphocytes that recognize lipid antigens presented by CD1d molecules and can rapidly produce large amounts of cytokines such as IFN-gamma upon activation, exerting direct cytotoxicity against tumor cells as well as modulating other immune populations in the tumor microenvironment[3][4]. PD-1+CD8+ T cells are a population of effector cytotoxic lymphocytes expressing the immune checkpoint receptor PD-1; these may be enriched for tumor-reactive or exhausted phenotypes. The rationale for combining these two populations is to leverage both direct anti-tumor activity (from both cell types), modulation of suppressive myeloid or stromal elements by iNKT-derived cytokines, and potential enhancement of endogenous anti-tumor immunity[3][4]. Clinical trials have demonstrated safety with only grade 1–2 adverse events reported (mainly fever, flu-like symptoms), no severe toxicities observed, and preliminary evidence for disease stabilization or partial response in advanced pancreatic cancer patients who had failed first-line chemotherapy[1][2][4]. This combination is being explored primarily in solid tumors such as pancreatic cancer and lung adenocarcinoma.

Other names

invariant natural killer T cell and PD-1 positive CD8 positive T cell combination therapyautologous iNKT and PD-1+CD8+ T cell immunotherapy