This review describes the published preclinical and clinical data on the use of a manual or semiautomated immunomagnetic selection device, termed the Isolex system. Preclinical evaluation of hematopoietic progenitor cells (CD34+ cells) selected from bone marrow, peripheral blood leukapheresis products, and umbilical cord blood is reviewed with respect to differentiation (CFU-GM, BFU-E, and CFU-GEMM formation) and proliferation. The purities and yields of CD34+ cell products from clinical trials performed since 1994 are presented along with data on malignant cell depletion. On average, the Isolex system resulted in a final product median purity of 67% and a final product median yield of 64%. Positive selection of CD34+ cells with this device decreased residual tumor cell levels by 2-3 logs in autologous transplant products and reduced T cell levels by 3-4 logs in allogeneic grafts. To evaluate the clinical effect of these immunomagnetically selected cells, data on the rate of engraftment were reviewed. Autologous CD34+ cell transplantation resulted in recovery time from neutropenia (ANC > 500/microliter) of 9-14 days and recovery time from thrombocytopenia (platelet count > 20,000/microliter) of 10-20 days. These data showed that the Isolex system can positively select progenitor cells to reconstitute the hematopoietic system following myeloablative therapy.
Two human monoclonal antibodies, directed against the type a and type b flagellar proteins of Pseudomonas aeruginosa, inhibited bacterial motility in vitro specifically and in a concentration-dependent manner. In order to determine if this decreased bacterial motility was associated with a decreased pathogenicity, the ability of these human antiflagellar monoclonal antibodies to attenuate P. aeruginosa-induced pneumonia in the rat was assessed. Incubation of P. aeruginosa with a 1:1 mixture of the human antiflagellar monoclonal antibodies prior to pulmonary instillation significantly (P < 0.05) ameliorated the bacterium-induced decrease in arterial blood oxygen pressure, blunted the increase in respiratory rate, and markedly reduced the area of pulmonary inflammation. Similarly, intravenous administration of the human antiflagellar monoclonal antibodies 1 h after pulmonary instillation of the bacteria also reduced the in vivo pathogenicity of P. aeruginosa. Therefore, human antiflagellar monoclonal antibodies can decrease the in vitro motility of P. aeruginosa and can reduce its in vivo pathogenicity when administered either before or after bacterial challenge.
The present study evaluated the effect of a novel anti-lipid A monoclonal antibody, termed SdJ5, on the in vitro production of tumor necrosis factor alpha (TNF-a) and interleukin-1f% by endotoxinor lipopolysaccharide (LPS)-challenged human peripheral blood mononuclear cells (hPBMC). In addition, the present study determined whether SdJ5 could neutralize the in vivo toxicity of LPS. SdJ5, at a concentration equal to or greater than 3 iLg/ml, specifically inhibited TNF-a and interleukin-lj production by hPBMC stimulated with every type of LPS and lipid A assessed. SdJ5 also showed a significantly greater inhibition of cytokine production than a nonrelevant human immunoglobulin M myeloma control. The SdJ5-mediated inhibition of TNF-a production was rapid, as the simultaneous addition of the SdJ5 and LPS still resulted in a marked decrease in hPBMC cytokine synthesis. The ability of SdJ5 to neutralize in vivo toxicity was also determined by using LPS from four different strains of gram-negative bacteria. LPS, when preincubated with SdJ5, resulted in a significant decrease in the 24-h mortality rate compared with that for the control. These studies show that the anti-lipid A monoclonal antibody SdJ5 can modulate LPS-induced cytokine production in vitro and increase the survival rate of rats challenged with lethal doses of LPS.
Chemicals leached from plastic blood bags are potentially immunogenic when introduced parenterally into humans. The experiments reported here represent an attempt to sensitize B6C3F1 mice to parenteral injections of solutions used to extract potentially immunogenic material from plastic blood bags. Mice were given intraperitoneal injections: blood bag extracts prepared from phosphate-buffered saline and ethanol; mouse red cells stored in extract solution; or blood bag extracts prepared from mouse serum. None elicited a significant in vitro immunologic reaction as determined by 3H-thymidine or 3H-leucine uptake into spleen cells. In contrast, intraperitoneal injections in mice of large amounts (0.5 ml) of the phosphate-buffered saline and ethanol extracts decreased spleen cellularity to 59 percent of the control value and reduced spleen cell blastogenic activity in vitro. When solutions of either mouse serum extract or mouse cells stored in extract were given intraperitoneally to mice, no spleen toxicity or increased blastogenic activity was observed. In addition, the extracts obtained from plastic blood bags by using either allogenic serum or buffered saline and ethanol did not elicit an immunologic response when they were administered parenterally to mice.
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