Induction of autoantibodies against mouse soluble proteins after immunization with living cells presenting the autoantigen at the cell surface in fusion with a human type 2 transmembrane protein

Induction of autoantibodies towards immune regulatory proteins, such as cytokines or their receptors, is a powerful strategy for functional studies on the role of these factors in vivo. Here we describe a new procedure to elicit autoantibodies by taking advantage of tumor cells as a vaccine against peptides presented at their surface in fusion with the human CD134L transmembrane protein. P1.HTR, an immunogenic variant of the P815 mastocytoma cell line, was used to generate stably transfected cell clones with expression vectors encoding the human CD134L transmembrane protein fused with either mouse IL-22BP or IL-9. Following repeated injections of living tumor cells expressing the mIL-22BP construct, mice developed autoantibodies that bind to mIL-22BP and inhibit its interaction with IL-22 in vitro. Mice similarly immunized against mIL-9 produced high titers of autoantibodies that block the activity of this cytokine in the TS1 bioassay. This procedure also inhibits IL-9 activity in vivo as no increase of serum MMCP-1 mast cell protease concentration was observed following IL-9 administration to immunized mice. As an alternative to the injection of living tumor cells expressing the CD134L-antigen fusion protein, intramuscular electrotransfer of the corresponding DNA construct also induced autoantibodies. These results validate this method as a simple and convenient approach to knock down the in vivo activity of soluble regulatory proteins, including cytokines and their receptors

Unusual cause of severe anaemia in a patient with metastatic haemangiopericytoma

Haemangiopericytoma is a rare tumor of vascular origin. We report the case of patient with severe refractory anaemia due to peripheral destruction of red blood cells by spleen metastases. Anaemia was successfully treated by splenectomy. Afterwards, our patient developed liver and lung metastases and was treated, in a clinical trial, with gefitinib that stabilised the disease during nine years. These interesting features are discussed

Sentinel lymph node imaging and research after bone scintigraphy in breast cancer patients

The aim of the study is to see if Bone Scan (BS) - when performed the day before the operation-interferes with the results of the Sentinel Lymph Node (SLN) technique using radiocolloids (their pre-operative imaging and their peroperative research). Therefore, the data of 393 patients who had one selective lymphadenectomy of the SLN(s) followed by the complete axillary node (AxN) clearance for Breast Cancer and among whom 309 patients had one BS the day before the operation (and just before the injection-s for the SLN) and 84 did not, were analysed and compared. The two series presented the same characteristics with regard to: age, clinical staging of the tumour, kind of injection-s performed (intradermic and paratumoural and/or intraparenchymal and peritumoral), pathological size of the tumour, percentage of cases with no AxN invasion, total number of AxN removed by the surgeons. The percentages of no axillary SLN visualisation, the mean numbers of axillary SLN visualised on preoperative lymphoscintigram as well as of SLN removed by the surgeons were not statistically different in the groups of patients with (respectively, 12.11, 2.6 and 3.03) and without BS (respectively, 12.99, 2.7 and 2.96). More noteworthy, the false negative (FN) rate of the SLN technique, albeit having a higher observed value in the group with BS (9.6%, 12/125), did not differ significantly from that in the group without BS (5.6%, 2/36). The accuracies (overall correct classification rates), the sensitivities and the negative predictive values of the SLN technique also did not differ significantly between the two groups. It is concluded that the SLN technique can be accurately performed just after one BS. © 2003 Elsevier Science Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

BrainStorm: A brain metastases research platform to tackle the challenge of central nervous system (CNS) metastases in solid tumors (Oncodistinct 006).

International audienceTPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text