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Biomedical subjects

Howard L Kaufman

Publications and source records attributed to Howard L Kaufman.

42 records · Page 3Linked to original sources

Prostate-specific antigen vaccines for prostate cancer.

Prostate cancer is the most common malignant tumour in men and there are few treatment options available once the tumour becomes refractory to hormonal manipulation. Prostate-specific antigen (PSA) is a secretory glycoprotein that is commonly expressed by prostatic epithelial cells and is found in elevated levels in the serum of men with prostate cancer. The identification of T cell specific epitopes within the coding sequence of PSA has led to the development of various vaccine strategies that target PSA in an attempt to treat established prostate cancer. These strategies have included human leukocyte antigen-restricted PSA peptides, dendritic cells pulsed with PSA, recombinant viruses expressing PSA and combinations of different vectors. In addition to PSA, several other antigens have been described that may be useful for targeting prostate tumours by vaccines. Animal studies have established the feasibility and safety for many of these agents and clinical trials are now in progress to evaluate the immunological and clinical responses of PSA vaccines. Further research in manipulating anti-PSA immunity with cytokines, costimulatory molecules and other immune modulating agents will likely improve the therapeutic effectiveness of PSA vaccines. Clinical trials designed to evaluate the effects of vaccination in different stages of disease and through different routes of administration need to be performed to define the optimal schedule for PSA vaccines in patients with prostate cancer, or for those at high risk of developing the disease.

Animals↗

CEA-based vaccines.

Carcinoembryonic antigen (CEA), the first tumor-associated antigen to be described, was cloned in 1987 and is expressed on nearly 50% of all human tumors. The identification of T-cell specific epitopes within the coding region of the CEA protein has led to the development of various vaccine strategies that target CEA and CEA-expressing tumors. These vaccines have shown evidence of therapeutic effectiveness in animal models and are being evaluated in early phase clinical trials. Although trials are not designed to elucidate clinical responses, they have provided important information about the ability of individual vaccines to induce CEA-specific immune responses through the use of newer in vitro monitoring assays. Continued clinical testing in patients with less advanced disease and the administration of vaccines in combination with other standard therapy will help define the role of CEA-based vaccines in the treatment and prevention of human cancer.

Animals↗

Immunotherapy for melanoma.

The immunogenicity of melanoma and the identification of melanoma-associated antigens is the basis for immunotherapy. This review will discuss the current status of melanoma immunotherapy with a focus on non-specific cytokines and highly specific vaccines, including peptides, viruses, dendritic cells, and whole cell vaccines. The passive transfer of melanoma-specific monoclonal antibodies and T-cells will also be reviewed. The problem of tumor escape and the association of immunotherapy to autoimmunity will be discussed. The use of immunotherapy in combination with other therapeutic agents and genetic profiling to predict responses suggests that immunotherapy will continue to play a role in the treatment of melanoma.

Adoptive Transfer↗

Surgical treatment of stage IV melanoma.

Surgical therapy plays an important role in the management of selected patients with metastatic melanoma. Patients are frequently symptomatic from metastatic lesions, have few effective therapeutic options, and are faced with dismal outcomes. Surgical resection may provide successful palliation of symptomatic lesions with low morbidity and operative mortality. In carefully selected patients, resections performed with curative intent may result in improved survival if a pattern of disease recurrence suggestive of favorable tumor biology is present, and if complete resection of tumor is achieved. Because the majority of post-surgical metastatic patients eventually relapse and succumb to distant disease, adjuvant immunotherapeutic strategies are currently being evaluated.

Adrenal Gland Neoplasms↗

Treatment of pediatric ocular melanoma with high-dose interleukin-2 and thalidomide.

Uveal melanoma is the most common primary ocular malignancy, although it is rare in children, and patients presenting with metastatic disease have a median survival of only 2 to 5 months. The tumor is generally unresponsive to systemic chemotherapy, but immunotherapy may be effective in selected patients. This report describes an 8-year-old girl with metastatic uveal melanoma treated with high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide. She tolerated treatment well and initially responded with stable disease in the liver and pancreas for 23 months. New pulmonary metastases developed and she was re-treated with high-dose IL-2, resulting in regression of her liver lesions and stable pulmonary disease for more than 18 months. These results suggest that IL-2 at high doses, and in combination with thalidomide, may be useful for uveal melanoma with tolerable side effects in children. Further study of this combination in children with immune-responsive tumors is warranted.

Angiogenesis Inhibitors↗