Mouse Anti-Human CD19 Monoclonal antibody, clone 4G7 Functional Grade

BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases (PM) is considered to be feasible, safe and to improve survival. AIM To investigate whether an immune response is activated following HIPEC for PM. METHODS Six patients were enrolled in this study. Peripheral blood samples were obtained from each patient prior to (day 0) and post-procedure (day 30), and used to evaluate the number of CD3(+) total, CD3(+)/CD4(+) T-Helper, CD3(+)/CD8(+) cytotoxic T, CD3(+)/CD56(+) natural killer and CD19(+) B lymphocyte numbers, and CD4(+): CD8(+) T lymphocyte ratios. RESULTS The total numbers of CD3(+), CD3(+)/CD4(+) T-Helper, CD3(+)/CD8(+) cytotoxic T, CD3(+)/CD56(+) natural killer and CD19(+) B lymphocytes, and CD4(+): CD8(+) lymphocyte ratios were increased in all but one patient 30 d following the cytoreductive surgery-HIPEC procedure, and these increases were significant (P <= 0.05) for CD3(+)/CD4(+) T Helper and CD3(+)/CD8(+) cytotoxic T lymphocyte numbers. CONCLUSION This report provides the first evidence that HIPEC exhibits immunomodulating activity in PM patients, resulting in generalized activation of the adaptive immune response. Moreover, the majority of lymphocyte populations increased following HIPEC and continued to be elevated several weeks following the procedure, consistent with a potential authentic immunomodulating effect rather than a normal inflammatory response, to be fully characterised in future studies.

CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9-24.9). Median follow-up after infusion was 7.1 months (0.5-42). BCA was observed 7 days after infusion (3-8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41-99) and 13% undetectable IgA levels at 185 days (11-308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.