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The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic,(More)
PURPOSE Bisphosphonates (such as risedronate and zoledronate) are widely used inhibitors of bone resorption. Despite their in vitro antiproliferative effects in various cancer cells, bisphosphonates have not exhibited significant antitumor efficacy in animal models of visceral cancer, which may be due to their poor bioavailability. The diagnostic use of(More)
Dendritic cells (DCs) are a central element in the development of antigen-specific immune responses. The lack of a specific and efficient technique for the in vivo delivery of antigens to DCs remains a major obstacle limiting a vaccine's ability to induce an effective immune response. The efficacy of adenoviral (Ad) vectors in this regard can be enhanced(More)
Low doses of the demethylating agent decitabine have been shown to enhance the sensitivity of tumors to immune effector cells and molecules through upregulation of tumor antigen presentation and apoptotic pathways. Effects on host immune effector and suppressor responses have not been well characterized. Mice bearing B16 melanoma were treated with low-dose(More)
We treated 23 patients with non-trophoblastic cancers with escalating doses of a synthetic vaccine consisting of the carboxy-terminal peptide of beta human chorionic gonadotropin conjugated to diphtheria toroid (CTP37), a muramyl dipeptide as an adjuvant, and squalene/mannide monooleate as a vehicle. Toxicity consisted of pain and sterile abscess formation(More)
Recombinant adeno-associated virus 2 (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. The potential of using rAAV as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. C57BL/6 mice received a single intramuscular injection of rAAV expressing the human(More)
The success of gene therapy depends on the specificity of transgene delivery by therapeutic vectors. The present study describes the use of an adenovirus (Ad) fiber replacement strategy for genetic targeting of the virus to human CD40, which is expressed by a variety of diseased tissues. The tropism of the virus was modified by the incorporation into its(More)
Apoptosis genes, such as TP53 and p16/CDKN2A, that mediate responses to cytotoxic chemotherapy, are frequently nonfunctional in melanoma. Differentiation may be an alternative to apoptosis for inducing melanoma cell cycle exit. Epigenetic mechanisms regulate differentiation, and DNA methylation alterations are associated with the abnormal differentiation of(More)
BACKGROUND Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma-detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG-72 can be identified in vivo. The immunologic characteristics of(More)
BACKGROUND Dendritic cells (DCs) are potent initiators of immune responses, and the infiltration of DCs into tumors may confer an improved prognosis. Whether the injection of DCs directly into tumors can mediate biologic activity was examined. METHODS Patients with metastatic dermal or subcutaneous tumors received granulocyte-macrophage-colony stimulating(More)