Purpose: Human CD40 ligand activates the malignant B-cell chronic lymphocytic leukemia cells and enhances their capacity to present tumor antigens. Human interleukin-2 further potentiates the immunogenicity of human CD40 ligand in preclinical murine models. Experimental Design: We prepared autologous B-cell chronic lymphocytic leukemia cells that expressed both human CD40 ligand (>90% positive) and human interleukin-2 (median secretion, 1,822 pg/mL/10 6 cells; range, 174-3,604 pg). Nine patients were enrolled in a phase I trial, receiving three to eight s.c. vaccinations. Results: Vaccinations were administered without evidence of significant local or systemic toxicity. A B-cell chronic lymphocytic leukemia^specific T-cell response was detected in seven patients. The mean frequencies of IFN-g, granzyme-B, and IL-5 spot-forming cells were 1/1,230, 1/1,450, and 1/4,500, respectively, representing a 43-to 164-fold increase over the frequency before vaccine administration. Three patients produced leukemia-specific immunoglobulins.Three patients had >50% reduction in the size of affected lymph nodes. Nonetheless, the antitumor immune responses were observed only transiently once immunization ceased. High levels of circulating CD4 + /CD25 + /LAG-3 + /FoxP-3 + immunoregulatory T cells were present before, during and after treatment and in vitro removal of these cells increased the antileukemic T-cell reactivity. Conclusions:These results suggest that immune responses to B-cell chronic lymphocytic leukemia can be obtained with human CD40 ligand/human interleukin-2^expressing s.c. vaccines but that these responses are transient. High levels of circulating regulatory T cells are present, and it will be of interest to see if their removal in vivo augments and prolongs the antitumor immune response.The malignant B-cell chronic lympocytic leukemia (B-CLL) cells express a range of tumor-associated and tumor-specific antigens, including immunoglobulins. These cells also express high levels of MHC class I and II molecules but lack costimulatory molecules and are ineffective antigen-presenting cells. Their immunogenicity can be increased by manipulation of the CD40/ CD40 ligand (CD40L) pathway, in which CD40L interacts with CD40 on B-CLL target cells to increase their antigen-presenting capacity through up-regulation of the costimulatory molecules CD80 and CD86 and adhesion molecules, such as CD54 (1 -5). CD40L also induces dendritic cell maturation in vivo, increasing their ability to take up and process antigens (6 -9). These effects have encouraged studies of CD40L as immunotherapy for human B-cell malignancies, with tumor responses and disease stabilization noted in both preclinical and clinical settings (1 -5, 10 -16). Using in vitro and in vivo models, we have shown that the immunostimulatory effect obtained with human CD40L

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Green peach aphid control was evaluated on greenhouse-grown calendula 12 Jun. The plants were in 4-inch pots evenly spaced on a greenhouse bench. Treatments were replicated 4 times in a randomized complete block design. The plants were sprayed until run-off with a Gilmore all-purpose trigger sprayer. A surfactant, Triton B 1956, was added to all treatments (3V2 oz/100 gal), except for the RH 7988 treatments for which Triton AG 98 was used (8 oz/100 gal). Infestations were determined by examining 4 leaves/plant and recording the total live aphids at 1, 7, and 14 DAT.

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