Use of tumor necrosis factor-alpha-coated gold nanoparticles to enhance radiofrequency ablation in a translational model of renal tumors.

OBJECTIVES: Radiofrequency ablation (RFA) has been most effective when the tumors are small, exophytic, and away from vital structures. We enlarged the size of the ablation kill zone by infusing a 30-nm tumor necrosis factor-alpha and polyethylene glycol-coated gold nanoparticle (CYT-6091, CytImmune Sciences, Inc.) before ablation in a rabbit kidney tumor model. MATERIALS AND METHODS: A total of 37 New Zealand White rabbits had VX-2 tumors implanted into their bilateral kidneys; they were then split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits as follows: (1) CYT-6091 only, (2) RFA only, (3) CYT-6091 followed 4 hours later by RFA. Gross and microscopic measurements of the ablation size as well as histologic analysis using hematoxylin and eosin staining were performed to determine the effect of CYT-6091 on the ablation. RESULTS: The RFA + CYT-6091 group had a larger zone of complete cell death than the RFA-only group when measured on microscopic examination (0.30 +/- 0.07 vs 0.23 +/- 0.03 mL, P = .03). The zone of partially ablated tissue was smaller in the RFA + CYT-6091 group than in the RFA-only group (0.08 +/- 0.02 vs 0.13 +/- 0.05 mL, P = .01). CONCLUSIONS: We have demonstrated the efficacy of CYT-6091 in enhancing RFA in a translational kidney tumor model. The potential usage of CYT-6091 to improve RFA of renal cell carcinoma merits further study.

Most highly exposed seronegative men lack HIV-1-specific, IFN-gamma-secreting T cells.

Naturally acquired cellular immunity in individuals who have been exposed to HIV-1 but have remained uninfected may hold clues for the design of an effective HIV vaccine. To determine the presence and nature of such an HIV-1-specific immune response, we evaluated the quantity and fine specificity of HIV-1-reactive IFN-gamma-secreting T cells in a group of highly exposed seronegative men having sex with men. All 46 ES reported frequent unprotected anal sex with known HIV-1-infected partners at enrollment, and high risk activities continued in at least one-half of the volunteers for up to >6 years of observation. Despite the high frequency of unprotected anal intercourse and potential HIV-1 exposure, the vast majority of individuals demonstrated no or very low numbers of HIV-1-specific, IFN-gamma-secreting T cells. Even when HIV-1 epitopes were presented by peptide-pulsed autologous dendritic cells in 15 of the highest risk volunteers, HIV-1-specific T cells remained infrequent, and the proportion of responders was not significantly different from that in a lower risk seronegative control cohort. Only PBMC from two individuals who have remained uninfected to date exhibited distinctly positive responses. However, these responses rarely persisted over time, single epitope specificities were identified in only one volunteer, and HIV-1-specific memory T cell clones did not expand in vitro. HIV-1-specific, IFN-gamma-secreting T cells are thus unlikely to substantially contribute to resistance against infection in most exposed seronegative men having sex with men.