Biomedical subjects

Albert F Lobuglio

Publications and source records attributed to Albert F Lobuglio.

3 recordsLinked to original sources

PubMed2006

TRAIL receptor-targeted therapy.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines. Based on its ability to induce apoptosis selectively in a wide variety of cancer cell lines and human tumor xenografts, TRAIL has been in drug development as a potential biological agent for cancer therapy. A variety of chemotherapy agents have been shown to enhance the cytotoxic effects of TRAIL. The potential benefits of TRAIL as an anticancer therapy have been further indicated by its ability to enhance the efficacy of radiotherapy. Preclinical studies have shown the potential use of agonistic monoclonal antibodies that selectively bind TRAIL death receptors for cancer therapy. This review provides an overview of TRAIL receptor-mediated apoptosis of tumor cells, with TRAIL or agonistic monoclonal antibodies only or with chemotherapy drugs. Treatment of tumor xenografts with these ligands, alone or in combination with chemotherapy or radiation, are discussed along with preliminary information about early clinical trials. Additional clinical trials with TRAIL receptor ligands in combination treatment regimens are required to determine their potential for targeted therapy of cancer.

Animals↗

PubMed2005

Intratumoral administration of a recombinant canarypox virus expressing interleukin 12 in patients with metastatic melanoma.

The aim of this study was to evaluate the tolerability and activity of intratumoral administered human interleukin 12 encoded by a vector derived from the canarypox virus (ALVAC-IL-12). Nine patients with surgically incurable metastatic melanoma who had subcutaneous nodules available for injection were enrolled. ALVAC-IL-12 was administered by intratumoral injection on days 1, 4, 8, and 11. Tumor nodules greater than 2 cm in diameter were injected with 2 x 10(6) median tissue culture infectious doses (TCID(50)), and smaller tumors were injected with 1 x 10(6) TCID(50). The total dose per patient per time point ranged from 1 x 10(6) to 4 x 10(6) TCID(50). Toxicity was mild to moderate and consisted of inflammatory reactions at the injection site and fever associated with chills, myalgia, and fatigue. No dose-limiting toxicities occurred. Increases in IL-12 mRNA, and also increases in interferon gamma mRNA, were observed in ALVAC-IL-12-injected tumors compared with saline-injected control tumors in four of the nine patients. ALVAC-IL-12-injected tumors were also characterized by T cell infiltration. Three patients demonstrated increases in serum IL-12 and in interferon gamma levels. All patients developed neutralizing IgG antibody to the canarypox vector. One patient manifested a complete response of injected subcutaneous metastases and uninjected in-transit metastases. The intratumoral injection of ALVAC-IL-12 at these dose levels and according to this schedule was well tolerated and resulted in measurable biologic response in patients with metastatic melanoma.

Adult↗

PubMed2003

History of antibody therapy for non-Hodgkin's lymphoma.

Monoclonal antibodies (mAbs) were the first successful targeted therapy for cancer. In contrast to the nonspecific nature of most chemotherapy, antibodies bind with high specificity to cell-surface antigens, resulting in targeted killing of malignant cells, relative sparing of normal tissues, and low toxicity. Antibody therapy has undergone substantial development since Ehrlich's notion of a "magic bullet," in 1890. It was not until the 1970s, however, that mAbs became viable as therapeutic tools and clinical studies showed them to be effective. The results were most impressive in hematologic malignancies, especially B-cell non-Hodgkin's lymphoma. In 1997, rituximab (Rituxan; Genentech Inc, South San Francisco, CA, and Biogen Idec Inc, Cambridge, MA) became the first mAb approved by the US Food and Drug Administration for use in the treatment of cancer. The first approval for a radiolabeled antibody to treat cancer was in 2002 for (90)Y ibritumomab tiuxetan (Zevalin; Biogen Idec). This is a conjugate of an anti-CD20 mAb (ibritumomab, the murine parent of rituximab) with the beta-emitter radionuclide (90)Y. (90)Y ibritumomab tiuxetan has been shown to be safe and effective in the indicated patient population. Other radioimmunoconjugates are being investigated for the treatment of non-Hodgkin's lymphoma, as are several immunotoxins. This article reviews important events in the development of mAb therapy and radioimmunotherapy for B-cell non-Hodgkin's lymphoma.

Antibodies, Monoclonal↗