Robert A. Stephenson

High Energy Shock Waves Suppress Tumor Growth in Vitro and in Vivo

Exposure of the Dunning R3327AT-3 rat prostatic carcinoma and SK-Mel-28 human melanoma, in vitro, to high energy shock waves resulted in a reduction in cell viability as determined by trypan blue exclusion and a decrease in the number of colonies formed in a clonogenic assay. Flow cytometric determination of DNA content in R3327AT-3 cells treated in vitro indicated a selective diminution of cells in the G2 and M phases of the cell cycle. When R3327AT-3 cells exposed to high energy shock waves were subsequently injected into rats, or tumor bearing animals were treated by high energy shock waves targeted at the tumor, a delay in tumor growth was observed. These observations indicate that high energy shock waves are cytotoxic to tumor cells in vitro and in vivo. Additional research into the possible use of high energy shock waves in the non-invasive destruction of animal and human tumors is warranted.

Quality of Life Following Prostatectomy as a Function of Surgery Type and Degree of Nerve Sparing

Objectives: To compare robotic-assisted laparoscopic prostatectomy with conventional retropubic radical prostatectomy in maintaining pre-surgery levels of urinary and sexual functioning and to evaluate the efficacy of nerve sparing in prostatectomies in protecting urinary functioning. Material and Methods: Patients (n = 385) receiving both surgical procedures were surveyed prior to surgery. Multiple measures, including the Expanded Prostate Cancer Index Composite, the Sexual Health Inventory for Men, and the International Prostate Symptom Score, assessed sexual and urinary function at an average of 12 months post-surgery. Results: Across multiple measures, while controlling for pre-surgical sexual functioning, robotic-assisted surgery did not offer an advantage in maintaining sexual or urinary function an average of a year following the prostatectomy. Bilateral nerve sparing offered a strong and reliable advantage in the maintenance of sexual function, but not so regarding urinary function. Conclusion: While robotic-assisted prostatectomies may offer a number of medical advantages over open procedures, we found no significant effect on important quality of life outcomes associated with the technique.

Abstract 594: Antibodies targeting LAG-3, TIM-3, KIR cloned from healthy human donors

The immunosurveillance/immunoediting theory postulates that tumor growth is repressed in healthy individuals through the activation of adaptive and innate immune mechanisms. The clinical success of antibodies that target inhibitory checkpoint pathways of the immune system (i.e. CTLA-4, PD-1) has provided compelling evidence in support of this theory and raises the question of whether antibodies targeting these, or other inhibitory immune cell modulators (ICM), are present in apparently healthy individuals. The present studies were designed to answer this question by probing the circulating memory B-cell compartment that represents a historic record of an individual9s lifelong adaptive immune response. Methods: Blood from donors, with no known cancer history, was screened for the presence of anti-ICM binding memory B-cells targeting LAG-3, TIM-3, B7-H3, KIR, and VISTA, using Trellis9s established CellSpotTM technology that can detect the presence of antigen specific memory B-cells at a frequency of 0.1 per 100,000 memory B-cells. Results: Circulating memory B-cells targeting ICM9s were present in all apparently healthy individuals tested (20 total). There was substantial variation as to which ICM9s were recognized within each individual across this sample population. Antibodies cloned from these rare B-cells were of IgG class and exhibited low to sub-nM affinity toward the specific ICM. These high affinity antibodies bound their respective antigens on activated T-cells and were able to augment immune stimulatory cytokine release in cellular assays. Data from ongoing studies will be presented. Conclusion: These studies demonstrate that apparently healthy individuals produce high affinity, pharmacologically active anti-ICM antibodies. Thus, healthy individuals represent a previously unrecognized source of antibodies that have undergone natural selection and hold particular promise as potential therapeutic agents for the treatment of cancer. Citation Format: Angeles Estelles, Robert Stephenson, Keyi Liu, Evelene Lomongsod, Da Ngyen, Jianzhong Zhzng, Yifan Yang, Manfred Heideker, Lawrence Kauvar, Stefan Ryser, Mikhail L. Gishizky. Antibodies targeting LAG-3, TIM-3, KIR cloned from healthy human donors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 594.