A monoclonal antibody raised against an undecapeptide sequence from human transforming growth factor alpha recognizes a hexapeptide epitope in mitotic centrosomes.

A monoclonal antibody (mAbIIa138) raised against the second-loop undecapeptide (residues [21-31]) of human transforming growth factor alpha, known to be involved in binding to its cell receptor, was found to define a hexapeptide epitope (RFLVQE, residues [22-27]). In enzyme-linked immunosorbent assay testing mAbIIa138 did not react with either native or reduced human transforming growth factor alpha, indicating that conformational restraints in this protein interfered with the antigenicity of the cognate sequence. Despite its failure to react with human transforming growth factor alpha, this monoclonal antibody proved very interesting when used to immunostain mammalian cells. mAbIIa138 was found to bind with great specificity to the centrosomes of late-interphase and mitotic cells. The staining of the centrosomes was most intense when the centrosomes were active in organizing the mitotic spindle and faded during telophase as the spindle was disaggregated. The epitope that mAbIIa138 recognizes is thus in a centrosomal protein, denoted CSP alpha, involved in some aspect of mitotic spindle organization or function. Analysis of the antigenic stringency of the epitope, using an amino acid replacement set, showed that 25 individual single amino acid replacements were possible without significant loss of antigenicity. Data bank searches for proteins of possible relevance were unsuccessful, so CSP alpha is an as yet unsequenced protein, specific to the centrosome.     

Dendritic cell immunotherapy for stage IV melanoma

Active boosting of the antitumour immune response of patients with solid malignancies has been tested in a large number of trials. Isolated complete clinical responses have been reported, however, they have not been replicated in subsequent studies. We recently reported objective clinical responses to a dendritic cell/irradiated autologous tumour cell 'vaccine' in patients with distant metastatic (stage IV) melanoma. Here we describe our experience in a second cohort of patients with stage IV melanoma, using this dendritic cell-based immunotherapy in a cryopreserved format. Of 46 patients enrolled into the study, three had complete remission of all detectable disease, and a further three had partial clinical responses. These data confirm that dendritic cell-based immunotherapy has potential as a therapy in a limited number of patients with stage IV melanoma. To our knowledge, this is the first demonstration that cryopreserved dendritic cells can elicit complete clinical responses in patients with advanced cancer. Our observations support randomized controlled trials to validate the findings.     

Search for “Weapons of Mass Destruction” for Cancer - Immuno/ Gene Therapy Comes of Age

The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromai cells and stem cells has so far prevented successful development and treatment of patients suffering from the later stages of cancers. At present, the use of conventional therapies, such as chemo/radio therapy is limited, and only therapies that are focused on utilizing the patient＇s immune response to combat against the disease appear to be the most reliable and promising. Two decades ago, cytokines were discovered to be able to activate the immune systems and mount an anti-tumour response. Then, dendritic cells were hailed as the most significant regulators of immunity and are employed in a variety of cancer management schemes. This review introduces current development in the field, focusing on combination of the components of ＇he rapidly growing fields of immunotherapy and gene transfer/therapy, providing useful and significant detailed information for readers of cellular and molecular immunology.     

Treating prostate cancer: a rationale for targeting local oestrogens

Prostate cancer is the most commonly diagnosed cancer and the second most common cause of cancer-related death in men, and benign prostatic hyperplasia is the most common benign condition known to occur in ageing men. Oestrogen has been implicated in the development of prostate cancer, and offers a promising new avenue for treatment. Despite this, the role of oestrogens in the prostate is complex. This Perspective presents a rationale for a targeted approach for the treatment of prostate disease through the use of selective oestrogen-receptor modulators in conjunction with contemporary androgen-ablation therapy.