The natural history of a novel, systemic, disseminated model of syngeneic mouse B-cell lymphoma

Abstract

Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics. Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics.

An NKT-mediated autologous vaccine generates CD4 T-cell–dependent potent antilymphoma immunity

“…All nonvaccinated mice after receiving 1 ϫ 10 6 live A20 cells died 4 to 6 weeks after tumor inoculation (Figure 2A), with massive tumor growth in liver, spleen, mesenteric lymph nodes, and bone marrow as reported. 23 Mice vaccinated with A20/veh showed similar pattern of survival (Figure 2A), supporting the nonimmunogenic properties of this tumor. 25 In sharp contrast, mice vaccinated with A20/␣GC were all 100% resistant to live A20 (Figure 2A).…”

In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy

“…Systemic B-cell lymphoma was induced by injection of 2 ϫ 10 6 A20 cells into the tail vein. 22 Twenty-four to 26 days after injection, 12 mice bearing disseminated A20 lymphoma and 6 age-matched healthy mice were subjected to the in vivo protein biotinylation procedure. All animal experiments were approved by the Swiss Federal Veterinary Office (license 198/2005).…”

“…The A20 lymphoma model is known to closely mimic histopathologic aspects and the anatomic distribution of large B-cell lymphoma in humans, recapitulating nodal and extranodal tumor growth in various organs. 22 Comparative proteomic analyses of lymphoma lesions and their corresponding host organs allowed the identification of a repertoire of differentially expressed bloodstream-accessible proteins. One highly promising candidate, BST-2, has been investigated in detail, revealing a restricted expression at lymphoma vascular sites, which could be targeted in vivo using anti-BST-2 antibodies.…”

Establishment of Leukemia Mouse Model Using Mouse-Derived A20 Leukemic Cells, and Detection of Tumor Cells in Bone Marrow

“…이외에 WEHI-3 (myelomonocytic), PU5-1R (myeloid) 등의 마우스 유래의 세포들을 이식하여 백혈병 모델로서 활용하였으며 특히 Balb/c (H-2 d ) 유래의 A20 세포주를 동일계통마우스에 이식한 동물모델은 이식편대 백혈병(graft-versus-leukemia; GVL) 연구와 항백혈병 면역 반응연구에 많이 이용되고 있다 (Glass et al, 1996;Zeis et al, 2001). A20 세포주는 이식 후 3-4주 후에 간 조 직에서 diffuse Large B-cell lymphoma가 형성되고 간조 직 외에도 근육 등 연조직, 복강, 비장 및 척추를 따라 산재성 림프종이 형성된 것이 보고되고 있다 (Passineau et al, 2005). 그러나 A20 세포주는 마우스 유래의 세포주 로서 CD45R 등의 B cell marker를 이용하여 말초혈액과 골수내에서의 종양세포 확장을 정확하게 판단할 수 없었 다.…”

“…그러나 A20 세포주는 마우스 유래의 세포주 로서 CD45R 등의 B cell marker를 이용하여 말초혈액과 골수내에서의 종양세포 확장을 정확하게 판단할 수 없었 다. 따라서 A20 세포주를 이용한 동물모델은 명확한 구 분이 없이 연구자에 따라 백혈병과 림프종 모델로 모두 사용되어 왔으며 림프종 모델로서 사용한 사례가 더 많 이 보고되고 있다 (Glass et al, 1996;Zeis et al, 2001;Xu et al, 1995;Passineau et al, 2005;Liu et al, 2007). A20 세포는 크기가 비교적 일정하고, 모양은 둥글고 표 면이 부드러우며 중심부는 검고 가장자리는 선명하게 보 이는 halo 현상이 관찰되었다( Figure 1A).…”