6533b85cfe1ef96bd12bbfe9

RESEARCH PRODUCT

An update on the xenograft and mouse models suitable for investigating new therapeutic compounds for the treatment of B-cell malignancies

Claudio TripodoFrancesco TedescoPaolo MacorSonia ZorzetClaudio CeleghiniErika Secco

subject

Lymphoma B-Cellmedicine.medical_treatmentChronic lymphocytic leukemiaAntineoplastic AgentsTargeted therapyNOAntineoplastic AgentB-cell malignanciesMiceDrug Delivery SystemsStromaSpecies SpecificityDrug DiscoverymedicineAnimalsHumansB-cell lymphomaMultiple myelomaB-cell malignancies; transgenic models; multiple myelomaPharmacologybusiness.industryAnimalCancerNeoplasms Experimentalmedicine.diseasePrimary tumorLeukemia Lymphocytic Chronic B-CellXenograft Model Antitumor AssaysLymphomamultiple myelomatransgenic modelImmunologyCancer researchB-cell malignanciebusinesstransgenic modelsDrug Delivery SystemHuman

description

B-cell malignancies account for over the 90% of all lymphoid neoplasms. The clonal proliferations of B-cells show a high degree of variation in terms of clinical and presenting features, histopathology, immuophenotype, and genetics. Primary tumor samples are useful for examining the characteristics of a patients own tumor, although both primary leukemic cells and cell lines provide an initial step for screening novel compounds for their activity in some hematological malignancies, they should be followed by models in intact animals. In this review, we try to summarize the animal models generated to study B-cell malignancies, in particular, B-cell lymphoma, B-cell CLL and MM that represent the major part of B-cell malignancies. Animals that spontaneously develop cancer are flawed to predict human disease. The development of human tumor xenograft models represented a big step towards more clinically relevant models. The major problems of these models are the requirement of immunocompromised animals and the inability of these models to recapitulate the complex relationship between the tumor and the microenvironment. A number of strategies have been also applied to develop genetically engineered models of malignancies, in which the tumor arises “naturally” in the host. The disadvantages of these models include the differences between rodent and human stroma and that they can not be used to characterise anti-tumor activity of many immunotherapeutic drugs. These models can be used to study the molecular processes critical for the development, proliferation and survival of hematological malignancies and to characterise potential therapeutic targets.

10.2174/138161208785294591http://hdl.handle.net/11392/2380335