2 research outputs found
Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells
Patients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Indeed, CIK cells are an effector population endowed with antitumor activity, which can be further improved and antigen-specifically redirected by clinical-grade mAb triggering antibody-dependent cell-mediated cytotoxicity
A specific antiâCOVIDâ19 BNT162b2 vaccineâinduced early innate immune signature positively correlates with the humoral protective response in healthy and multiple sclerosis vaccine recipients
Abstract Objectives The very rapidly approved mRNAâbased vaccines against SARSâCoVâ2 spike glycoprotein, including PfizerâBioNTech BNT162b2, are effective in protecting from severe coronavirus disease 2019 (COVIDâ19) in immunocompetent population. However, establishing the duration and identifying correlates of vaccineâinduced protection will be crucial to optimise future immunisation strategies. Here, we studied in healthy vaccine recipients and people with multiple sclerosis (pwMS), undergoing different therapies, the regulation of innate immune response by mRNA vaccination in order to correlate it with the magnitude of vaccineâinduced protective humoral responses. Methods Healthy subjects (n =â20) and matched pwMS (n =â22) were longitudinally sampled before and after mRNA vaccination. Peripheral blood mononuclear cell (PBMC)âassociated type I and II interferon (IFN)âinducible gene expression, serum innate cytokine/chemokine profile as well as binding and neutralising antiâSARSâCOVâ2 antibodies (Abs) were measured. Results We identified an early immune module composed of the IFNâinducible genes Mx1, OAS1 and IRF1, the serum cytokines ILâ15, ILâ6, TNFâα and IFNâÎł and the chemokines IPâ10, MCPâ1 and MIG, induced 1âday post second and third BNT162b2 vaccine doses, strongly correlating with magnitude of humoral response to vaccination in healthy and MS vaccinees. Moreover, induction of the early immune module was dramatically affected in pwMS treated with fingolimod and ocrelizumab, both groups unable to induce a protective humoral response to COVIDâ19 vaccine. Conclusion Overall, this study suggests that the vaccineâinduced early regulation of innate immunity is mediated by IFN signalling, impacts on the magnitude of adaptive responses and it might be indicative of vaccineâinduced humoral protection