Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Current and Emerging Treatment Options for Castration-Resistant Prostate Cancer: A Focus on Immunotherapy

BACKGROUND: Castration-resistant prostate cancer is a disease with limited treatment options. However, the ongoing elucidation of the mechanisms underlying this disease continues to support the development of not only novel agents, but also innovative approaches. Among these therapies, immunotherapy has emerged as a promising strategy. DESIGN: This review article summarizes the most recent data from investigations of immunotherapies in castration-resistant prostate cancer (literature and congress searches current as of August 2011). RESULTS: Immunotherapeutic strategies such as passive immunization, vaccines, and particularly checkpoint blockade have demonstrated some efficacy as single agents. Elucidation of effective combinations of agents and drug regimens is ongoing but will require continued careful investigation, including the standardization of surrogate endpoints in clinical trials. CONCLUSIONS: It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity

A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies

INTRODUCTION: The clinical efficacy of trastuzumab and taxanes is at least partly related to their ability to mediate or promote antitumor immune responses. On these grounds, a careful analysis of basal immune profile may be capital to dissect the heterogeneity of clinical responses to these drugs in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. METHODS: Blood samples were collected from 61 locally advanced breast cancers (36 HER2- and 25 HER2+) at diagnosis and from 23 healthy women. Immunophenotypic profiling of circulating and intratumor immune cells, including regulatory T (Treg) cells, was assessed by flow cytometry and immunohistochemistry, respectively. Serum levels of 10 different cytokines were assessed by multiplex immunoassays. CD8+ T cell responses to multiple tumor-associated antigens (TAA) were evaluated by IFN-γ-enzyme-linked immunosorbent spot (ELISPOT). The Student's t test for two tailed distributions and the Wilcoxon two-sample test were used for the statistical analysis of the data. RESULTS: The proportion of circulating immune effectors was similar in HER2+ patients and healthy donors, whereas higher percentages of natural killer and Treg cells and a lower CD4+/CD8+ T cell ratio (with a prevalence of naïve and central memory CD8+ T cells) were observed in HER2- cases. Higher numbers of circulating CD8+ T cells specific for several HLA-A*0201-restricted TAA-derived peptides were observed in HER2+ cases, together with a higher prevalence of intratumor CD8+ T cells. Serum cytokine profile of HER2+ patients was similar to that of controls, whereas HER2- cases showed significantly lower cytokine amounts compared to healthy women (IL-2, IL-8, IL-6) and HER2+ cases (IL-2, IL-1β, IL-8, IL-6, IL-10). CONCLUSIONS: Compared to HER2- cases, patients with HER2-overexpressing locally advanced breast cancer show a more limited tumor-related immune suppression. This may account for the clinical benefit achieved in this subset of patients with the use of drugs acting through, but also promoting, immune-mediated effects

Abstract P5-16-06: A phase 2 randomized trial of docetaxel (DOC) alone or in combination with therapeutic cancer vaccine, CEA-, MUC-1-TRICOM (PANVAC)

Abstract Background: A previous phase 1/2 trial of PANVAC, a poxviral based cancer vaccine, suggested clinical efficacy in some patients (pts) with breast and ovarian cancer and evidence of immunologic activity. Preclinical data showed DOC can modify tumor phenotype, making tumor cells more amenable to T-cell mediated killing. The goal was to determine if DOC and PANVAC could synergize and improve clinical outcomes compared with DOC alone. Methods: This is an open-label randomized phase 2 multi-center trial designed to enroll 48 pts with metastatic breast cancer to receive DOC in combination with PANVAC (A) or alone (B). Cross-over was allowed so that pts randomized to B could receive the vaccine upon progression. Eligibility included ECOG performance status &amp;lt;1 and normal organ and immune function with no limits on previous lines of therapy, but pts may not have received DOC for metastatic disease. Her2+ pts on trastuzumab were allowed to continue trastuzumab on trial. All pts received DOC 35mg/m2 weekly × 3 doses during 28-day cycles. Pts on A were “primed” with recombinant vaccinia-PANVAC study day 1. Three weeks later, they began 28-day cycles of DOC with “boost” recombinant fowlpox-PANVAC given on day 1, given until progression. CT and bone scans were performed after 3 cycles and then every 2 cycles. 1° endpoint was PFS., with a phase 2.5 statistical design, with the intent of identifying a trend toward benefit to guide a larger trial design. A p value of 0.10 is considered a strong trend. 2° endpoints included overall survival and immunologic correlative studies. Immunologic assays included analysis of T cell and NK cell activation, presence and activity of regulatory T cells, and ELISPOT assays. Immune correlative analysis was done using multiparametric flow cytometry analysis of immune cell subpopulations from peripheral blood mononuclear cells (PBMCs) of pts and comparing those findings using Boolean logic with the immune assays and clinical outcomes. Results: Enrollment of 48 pts completed in February 2012 (A, n=25; B, n=23). Five pts remain on treatment (2 on A, 3 on B). Pt and tumor characteristics were well matched. Analysis through August 2, 2012 (median follow-up of 5.1 months for pts on study), indicates PFS is 6.6 vs. 3.8 months in A vs. B (p = 0.12, HR=0.67, 95% CI: 0.34 to 1.31). Analysis of the adverse events on both arms demonstrated very little difference between the two groups. The only statistically significant differences were increases in the frequency of grade 1 and 2 edema (p = 0.018) and injection site reactions (p &amp;lt;0.0001) in the combination arm. Immune analysis and correlation to pt clinical outcomes are ongoing and will be available for presentation at the time of the meeting. There are not yet enough events to perform a comparison of overall survival in the two groups. Conclusion: This randomized study suggests the combination of PANVAC with DOC in metastatic breast cancer may provide a clinical benefit compared to DOC alone. The clear separation of the curves indicates potential benefit, which is not statistically significant, likely due to the small number of pts enrolled. This study was hypothesis generating and may provide both rationale and statistical assumptions for a larger definitive randomized study. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-06.</jats:p