Objective To investigate cancer immunotherapy using whole allogeneic (differing tissue‐type) tumour cells as vaccines in the rat prostate cancer model. Materials and methods Two rat models of prostate cancer were used; MAT‐LyLu tumours which grow in Copenhagen rats and PAIII tumours which grow in Lobund–Wistar rats, with crossover of the cell lines to test allogeneic vaccination. The cell lines were immunologically characterized by flow cytometry. Irradiated tumour cells were administered as subcutaneous vaccines either before tumour challenge or after tumour establishment (both subcutaneous). A preparation of heat‐killed Mycobacterium vaccae bacilli (SRL172) was used as an adjuvant to increase vaccine efficiency. Results Flow cytometry analysis of the cell lines showed that the PAIII cells had higher levels of major histocompatibility complex (MHC) class I and intercellular adhesion molecule (ICAM‐1) expression than the MAT‐LyLu cells. However, both tumour cell lines were rejected in their allogeneic hosts. Prophylactic vaccination with allogeneic MAT‐LyLu cells protected against PAIII tumour challenge in Lobund–Wistar rats, with 80% of animals surviving for > 5 months, compared with 40% for animals receiving autologous cells. The immunity was prolonged, as rats were protected when rechallenged 5 months later. In Copenhagen rats allogeneic PAIII cells protected against the more aggressive MAT‐LyLu tumour challenge only when the cells were combined with SRL172. Initial therapy experiments showed that vaccination with the cell lines mediated only limited tumour regression in the Lobund‐Wistar rats. Conclusion The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.
Psoriasis is a long‐lasting disease involving inflammation of the skin. In the most common form of this disease ‐ plaque psoriasis ‐ the inflammation is visible as raised, reddened and often scaly areas which may extend widely over the body. Although not generally a life‐threatening condition, psoriasis may increase the risk of other serious disorders (such as cardiovascular disease), and often leads to much reduced quality of life for patients ‐ through physical discomfort (itching, pain), disability, and related emotional trauma. Furthermore, psoriasis occurs worldwide (affecting up to 3% of the populations in various countries) and cannot be completely cured by available treatments. Together, these issues make the disease a serious global burden. Granulocyte‐Macrophage Colony‐Stimulating Factor (GM‐CSF) is made in the body and is important in controlling functions of the body's immune system and the processes involved in inflammation. Therefore, this study was carried out to establish whether blocking the activities of GM‐CSF in patients with moderate or severe plaque psoriasis could result in significant improvement of the disease. In total, 122 patients were enrolled from Canada, Denmark, Germany, Latvia and Poland. The patients were treated over 10 weeks either with namilumab (GM‐CSF blocker) or a placebo (inactive): assessments of their psoriasis were made during this period, and completed after an additional 2 weeks. Notably, throughout the 12‐week study duration no significant improvement was detected for namilumab‐treated patients ‐ in marked contrast to treatment benefit found in a similar study involving patients with rheumatoid arthritis. These findings point to different roles for GM‐CSF in the two diseases, and suggest that blocking GM‐CSF activity alone is not enough for effective treatment of plaque psoriasis.
Abstract A retrospective case-control study was carried out on 230 patients with multiple sclerosis (MS) and 230 controls matched for year of birth and sex. The geographical distribution of residence of MS patients and controls was similar. Two peak ages of onset of MS were observed among woman patients (20–24, 30–34 years). There was no difference in histories of infectious diseases and autoimmune diseases between the two groups. A greater number of hairdressers was noticed among the patient group (p < 0.05) and three patients (no control) had had professional contact with pathology specimens.
Since there is much indirect evidence for dominant suppressor genes for melanoma, we sought to isolate such a gene. Metastatic B16–F10 murine melanoma cells were lipofected with a normal human genomic library in a cosmid vector that also confers resistance to the drug G418. A few of the G418-resistant colonies acquired combinations of properties resembling those of normal melanocytes, including differentiated features (pigmentation, dendriclty), slower growth, flat shape, monolayered colony form, stimulation of proliferation by a phorbol ester, and anchorage dependence. Four out of eight also showed reduced tumorigenicity in mice. Southern blotting indicated the presence of numerous cosmids in the melanocyte-like transfectants. DNA from one such line was used for secondary transfection. One secondary G418-resistant line showed pronounced melanocytic properties and marked tumour suppression in syngeneic and nude mice. A human repetitive sequence detected in this line was used in the polymerase chain reaction (PCR) to isolate intervening unique DNA sequences. One unique human sequence was attenuated in all tumours arising from both primary and secondary transfectants, suggesting close linkage with the sequence responsible for tumour suppression.
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