J Nemunaitis

..This phase I-II study evaluated the safety, clinical activity and immunogenicity of an immunotherapy developed from human prostate cancer cell lines (PC-3 and LNCaP) modified to secrete granulocyte-macrophage colony-stimulating factor...

..Evidence of antitumor activity is suggested and may correlate with histone modulation...

..The rationale of GVAX development and a summary of clinical results are reviewed...

..The purpose of this study was to determine the maximum tolerated dose, pharmacokinetic profile, and evidence of antitumor activity of CI-994 used in combination with gemcitabine...

..Modifications may one day enable more aggressive use of these new and exciting therapeutics as systemic gene delivery vehicles...

..These results supported further clinical investigation with GVAX in non-small cell lung cancer...

..e. able to convert 5-FC to 5-FU) at doses at or below 3 x 10(7) CFU/m(2)...

..This review will summarize phase I and II trial results. Conclusions drawn from these studies justify the currently ongoing phase III investigation...

..Preliminary Phase I and II results suggest evidence of efficacy and justify accrual Phase III trials, which are currently ongoing...

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..028), suggesting a vaccine dose-related survival advantage...

..To determine maximum tolerated dose (MTD) and evidence of antitumor activity of topotecan in combination with gemcitabine in refractory cancer patients...

..Survival of melanoma patients with an IL-10 level above 10.0 pg/ml was 365 days compared to 557 days in patients with IL-10 levels less than 10.0 pg/ml (p = 0.0259, Wilcoxon). Elevated IL-10 levels were correlated with poor survival...

..To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN)...

..This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer...

..To determine the toxicities, dose-limiting toxicities (DLT), maximum-tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with advanced solid tumors...

..Further investigation of ONYX-015, possibly with agents that may modulate replication activity, or duration of virus survival, is indicated...

..The intravenous administration of genetically altered adenovirus is a feasible approach...

..To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC)...

..0462, Wilcoxon; p = 0.0273, log rank). We conclude that intratumor injection of IFN-gamma is safe and well tolerated. Evidence of antitumor activity is suggested in patients with advanced malignancy that received multiple injections...

..A larger clinical trial is warranted to further explore this observation...

..Area under the curve determinations indicate a marked higher level of TNF-alpha induction and accelerated clearance at cycle 2 in the absence of enbrel. Further assessment is recommended...

..Growth inhibition through the reconstitution of miRNAs is potentially applicable for experimental therapy of prostate cancer, pending molecular validation of targeted genes...

..The major challenge for researchers is to maximize the efficacy of these viral therapeutics, and to establish stable systemic delivery mechanisms...

..The bifunctional shRNA is a highly effective and advantageous approach mediating RNAi at concentrations significantly lower than conventional shRNA or siRNA. These results support further evaluations...

..We identified no tumor responses of the injected lesions. Of 13 patients with advanced melanoma, 6 survived over one year. Thus, injection of retroviral delivered HSV-TK in patients with refractory cancer was well-tolerated...

..This review considers comparisons of the off-target effects of siRNA to shRNA and their potential impact on the efficacy and toxicity of RNAi based therapeutics...

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..Here, the authors report an initial clinical study of the safety and tolerability of an intravenous infusion of ISIS 2503 in patients with advanced cancer...

..The aim of this study was to determine the efficacy and safety of talabostat in NSCLC patients...

..However, the frequency of vaccine site reactions, tumor response, time to disease progression, and survival were all less favorable in the current study...

..Specific vaccines fulfilling justification for Phase III evaluation based on these results include LBLP25, TGF-beta2 antisense gene vaccine and GVAX...

..Further animal safety testing followed by clinical study is recommended...

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..This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment...

..We performed a retrospective study to characterize better this new treatment modality...

..Preclinical and early clinical results presented indicate a high safety profile and demonstrate clear anticancer activity, thereby justifying further investigation of bacteria as a therapeutic approach in the treatment of cancer...

..These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the "bench to the bedside."..

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..Plasma biomarkers HER2, vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-9 were evaluated using immunologic techniques...

..The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity...

..Safety has been confirmed and despite variable efficacy results several dramatic responses have been observed with some oncolytic viruses. This review summarizes results of clinical trials with oncolytic viruses in cancer...

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..The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade...

..Patients with metastatic NSCLC who had previously failed chemotherapy demonstrated response to GVAX (3 of 33 complete responses) and dose-related improvement in survival (471 days vs. 174 days)...

..This article explores the principles of viral therapy for cancer and the past several decades of investigations with viruses such as Egypt 101, mumps, Newcastle disease, influenza, vaccinia, herpes simplex, and adenovirus serotype 5...

..In this review, we survey a sampling of current therapeutic approaches that depend upon adenoviral delivery vehicles and outline the advantages and disadvantages of this vector system...

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..Thus intratumoral administration of INGN 241 is well tolerated, induces apoptosis in a large percentage of tumor cells, and demonstrates evidence of clinically significant activity...

..8 months median duration of response. Allovectin-7 was shown to be safe and exhibit biological activity at this dose. Its safety profile may enable Allovectin-7 to be used at higher doses, which may provide greater clinical activity...

..These findings indicate that Internavec can generate a two-pronged attack on tumor cells through oncogene knockdown and viral oncolysis, resulting in a significantly enhanced antitumor outcome...

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..To determine the tolerability and pharmacokinetics of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, administered over 14 consecutive days of a 21-day cycle...

..Results of preclinical studies justify clinical investigation. A summary of clinical results is presented...

..Three patients with complete regression have survived > or = 2 years from the time of treatment. CONCLUSIONS: Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials...

..In conclusion, we recommend further investigation of oral topotecan (1.5 mg/m2/d(-1)) on days 1 to 5 of each week for 2 weeks in combination with capecitabine (180 mg/m2 twice daily) on days 1 to 14 within a 21-day cycle...

..Further studies are needed to demonstrate whether these novel therapies can potentially complement or replace current therapeutic approaches...

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..Intratumoral delivery of INGN 241 induced apoptosis in a large volume of tumor and elicited tumor-regulatory and immune-activating events that are consistent with the preclinical features of MDA-7/IL-24...

..Results suggest a high level of safety but evidence of L523S-directed immune activation was limited, suggesting a need for modification of dose, schedule, and site of vaccination (i.e., intradermal) with further clinical testing...

..Belagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition...

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..Here, we review the most promising current nonviral gene delivery vehicles with a focus on their potential use in cancer shRNA therapeutics...

..Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy...

..The evaluation of miRNAs expression may also be of prognostic value, as best exemplified by the correlation of let-7 and mir-155 levels with disease survival in nonsmall cell lung cancer...

..The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi...

..The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene...

..Such evidence supports the strategy of individualised selection of a therapeutic complex from a menu of targeting options that best complements the specific oncomolecular profile of the 'tumour-host' system...