Strategies for Cancer Vaccine Development

Treating cancer with vaccines has been a challenging field of investigation since the 1950s. Over the years, the lack of effective active immunotherapies has led to the development of numerous novel strategies. However, the use of therapeutic cancer vaccines may be on the verge of becoming an effective modality. Recent phase II/III clinical trials have achieved hopeful results in terms of overall survival. Yet despite these encouraging successes, in general, very little is known about the basic immunological mechanisms involved in vaccine immunotherapy. Gaining a better understanding of the mechanisms that govern the specific immune responses (i.e., cytotoxic T lymphocytes, CD4 T helper cells, T regulatory cells, cells of innate immunity, tumor escape mechanisms) elicited by each of the various vaccine platforms should be a concern of cancer vaccine clinical trials, along with clinical benefits. This review focuses on current strategies employed by recent clinical trials of therapeutic cancer vaccines and analyzes them both clinically and immunologically

Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus.

Abstract BACKGROUND: The development of oesophageal adenocarcinoma is generally closely associated with the presence of a specialised intestinal-type epithelium such as that found in Barrett's oesophagus (BO). A particular histological condition is when the distal oesophagus showing cardiac and/or fundic mucosa without intestinal metaplasia cannot be defined as 'Barrett's mucosa' [condition that we call 'columnar-lined oesophagus' (CLO)] and up till now, there has been no agreement in literature about the management of this condition. Aurora-A overexpression leads to centrosome amplification, chromosomal instability and aneuploidy in mammalian cells. PATIENTS AND METHODS: A prospective study was carried out on 28 consecutive patients who presented columnar mucosa above the gastro-oesophageal junction (GOJ) at endoscopy. As controls, two more biopsies were obtained, one on the normal-appearing squamous oesophagus above the GOJ, as far as possible from the columnar mucosa (controls A), and one taken 1 cm below the GOJ (controls B). The Aurora-A and p53 expression levels were analysed respectively by Quantitative Real Time PCR and immunohistochemistry. RESULTS: Twelve patients were affected by BO (43%) while the other 16 patients (57%) had a CLO. Nine of 28 (32%) cases were focally positive for p53 immunostaining. All the BO/CLO samples were positive for the Aurora-A transcript with regard to controls. Furthermore, 13 of 28 (46%) cases showed overexpression (above the median for the whole group). CONCLUSION: Due to the low number of cases, we are not at present able to state that statistically significant quantitative differences in Aurora-A messenger RNA expression exist between CLO and BO cases with and without dysplasia and p53-positive immunostaining. Further studies on a larger number of cases with a follow-up period are necessary in order to establish the risk of progression and the correct management of these subjects

BRCA1 genetic testing in 106 breast and ovarian cancer families from southern Italy (Sicily): a mutation analyses.

PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total of 106 unrelated families affected with breast and/or ovarian cancer screened for mutations occurring in the whole BRCA1 gene by automatic direct sequencing. RESULTS: Germline BRCA1 mutations were found in 17 of 106 (16%) Sicilian families. The HBOC profile had a major frequency (66%) of mutations (P < 0.01). A total of 28 sequence variants was identified. Seven of these were pathogenic, 5 unknown biological variant (UV) and 16 polymorphisms. We also identified a pathological mutation (4843delC) as a possible Sicilian founder mutation. CONCLUSIONS: The present study is the first BRCA1 disease-associated mutations analysis in Southern Italian families. The early age of onset of such tumors and the association with the HBOC familial profile could be two valid screening factors for the identification of BRCA1 mutation carriers. Finally, we identified a BRCA1 mutation with a possible founder effec

A case of guillain-barre syndrome in a patient with non small cell lung cancer treated with chemotherapy

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating polyneuropathy. Specific therapy with intravenous immunoglobulin 25 g/day in 5 administrations for 5 days was started with complete benefit