Lymphoma Xenograft

Altogen Labs validated Lymphoma Xenograft animal models:

A20,  Raji,  EL4DOHH2KARPAS299,  Ramos

Xenotransplantation studies have been a backbone of oncology research for four decades, and provide an effective research and evaluation environment for novel pharmaceutical compounds. Typically, these studies involve the implantation of tumorigenic human cell lines into immunocompromised mice, providing scientists with an in vivo model of tumor behavior in which to perform experiments including screening of novel cancer therapies, studies of cell behavior, and examination of metastasis. Patient-derived xenografts are a fundamental part of in vivo pharmacological research, aiding in the translation from benchtop to bedside.

Lymphoma describes a type of cancers that develops from white blood cells, or lymphocytes. Symptoms include enlarged lymph nodes (lymphadenopathy), sweating, fever, weight loss, fatigue and itching. Risk factors include autoimmune diseases, HIV/AIDS, smoking and the Epstein-Barr virus. There are two main types of lymphomas (and dozens of subtypes) which are non-Hodgkin lymphomas (NHL) and Hodgkin’s lymphomas (HL). NHL accounts for most occurrences of lymphoma and are an umbrella term for a wide variety of lymphomas which are categorized by the WHO classification which account for cytogenetic, phenotypic and molecular characteristics. Prognosis varies greatly by specific subtype, for example small lymphocytic lymphoma is relatively indolent while Burkitt’s lymphoma is aggressive with rapid health deterioration. Subtypes include Mature T-cell, B-cell, natural killer cell and precursor lymphoid neoplasms as well as immunodeficiency-associated lympthoproliferative disorders. A biopsy by a pathologist or hematopathologist can help diagnose the specific subtype and appropriate treatment. Histopathological features are typically determined by immunophenotyping, flow cytometry or fluorescence in situ hybridization. Also relevant is the site from which the lymphoma originates. Lymphomas are known to spread to the CNS, and when spread to the meninges of the brain is known as lymphomatous meningitis (LM). CT scans or PET scans are often used to determine the stage of the cancer and how many lymph nodes or other tissues are affected. Treatment depends on the classification of the lymphoma as low-grade or high-grade. Low-grade lymphomas are known to remain indolent for years but are incurable. Treatments are generally only considered for patients who display symptoms (which is not always the case) and can include chemotherapy, radiotherapy or lymphadenopathy. High-grade lymphomas are aggressive but can be cured with aggressive chemotherapy (CHOP or R-CHOP) however a relapse results in poor prognosis. For relapse patients aggressive chemotherapy combined with autologous stem cell transplantation has seen success. Hodgkin type lymphoma requires chemotherapy (or standalone radiotherapy for localized cases). Popular regimens include ABVD or BEACOPP. The 5-year survival rate for localized lymphomas is 82% while for metastasized lymphomas it is 63%, although these numbers depend on a variety of factors as there are so many subtypes of lymphoma.

Using human xenograft models of lymphoma, as previously mentioned, is a powerful research tool, and there are several models of lymphoma to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, summarized in the table below. Models are often selected based on morphology, genetics, histology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). The goal of xenografts and murine models is to mirror human pathology and disease as closely as possible so that accurate insights into cellular events are achieved. This aspect is particularly critical with preclinical drug testing for accurately evaluating compound efficacy.

Cell Line Characteristics
A20 ·    Murine cell line derived from a spontaneously developed reticulum sarcoma (BALM/c mouse)

·    Expresses PD-L1 and surface immunoglobin

·    Used to study NHL B-cell lymphoma

EL4 ·    Murine cell line isolated from a chemically induced lymphoma

·    Used in immunological research

·    Expresses IL-4 and Thy-1.2 antigen

·    Resistant to dexamethasone, BUdR and cortisol

DOHH2 ·    Human cell line from the pleural effusion of a lymphoma patient

·    Overexpresses BCL-2

·    NHL B-cell lymphoma

·    Contains the Epstein-Barr virus

·    Expresses CD10, 19, 20 and 37

KARPAS 299 ·    Human line established from the peripheral blood of a NHL patient

·    Aggressive anaplastic large cell lymphoma (ALCL) subtype

·    ALK-positive

Raji ·    Hemapoietic human cell line from a Burkitt’s lymphoma (left maxilla) patient

·    B-cell lymphoma expressing CD20, 46, 52, 147 and 19

·    Positive for Epstein Barr virus (EBV)

·    Male diploid karyotype

·    Partially resistant to vesicular stomatitis viruses (VSV) and poliovirus

Ramos ·    Human cells isolated from a Burkitt’s lymphoma patient

·    Used to study antibody mediated therapy

·    Positive for CD23, immunoglobin and IL4

·    No traces of EBV in genome

Altogen Labs is one of the leading biology contract research organization (CRO) based in Austin, Texas. Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of human tumor xenografts for research and clinical purposes. Altogen Labs offers a complete suite of laboratory services, including:

  • xenotransplantation study design
  • selection of appropriate cancer model/cell line
  • host animal selection
  • subcutaneous or orthotopic xenografting
  • daily observation of experimental subjects
  • post-experiment analysis, including serum collection and histology

Mouse strains available at Altogen Labs:

Mouse type T cells B cells NK cells Coat Other Notes
CD1 No Yes Yes White/albino Outbred
B6 Yes Yes Yes White/albino Inbred
Balb/c No Yes Yes Nude, albino Inbred
Balb/SCID No No Yes White Inbred
NOD/SCID No No Impaired White Inbred
Nu/nu No Yes Yes Nude Outbred
CD57BL Yes Yes Yes Dark brown/black Inbred
CB17 Yes Yes Yes White Inbred
NSG No No No White Inbred
Swiss Nude No Yes Yes Nude Outbred

 

About the models

CD1

This model originates from a non-inbred Swiss stock of the 1920s from the Centre Anticancerux Romand (Lausanne, Switzerland). Outbred stocks are generally used for their genetic variability.

B6

This strain of mouse arose from a spontaneous mutation in the C57BL/6 strain resulting in a coisogenic albino mutant. These mice have a mutant tyrosinase gene.

Balb/c

This strain of nude mouse was developed in the 1980s through many crosses and backcrosses and remains to be an inbred model. Balb/c mice do not have a thymus and therefore cannot produce T-cells and are considered immunodeficient. Balb/c mice are often used for their easy breeding and similar weights (low-variation) of males and females. They are also used for monoclonal antibody production.

Balb/SCID

This mouse model lacks functioning T and B cells but do have functioning NK cells which limits engraftment. These mice are sensitive to irradiation and have functioning macrophages, dendritic cells and complement activity. Some cancer cell lines show improved engraftment over nude models in Balb/SCID mice.

NOD/SCID

The homozygous SCID mutation results in impaired T cell and B cell lymphocyte development. The NOD characteristic results in impaired natural killer cell function. NOD/SCID mice also lack macrophage and dendritic cell activity as well as reduced complement activity. These mice have a non-obese diabetic and insulitis background and low cytokine production. NOD/SCID mice exhibit a 36-week median survival due to the development of thymic lymphomas, which limits their use to short-term experiments.

Nu/nu

These mice originate from the National Institute of Health (NIH). Originally thought to be BALB/C congenic mice, once it was discovered that these mice were outbred they were determined to be of their own strain. These mice do not have a thymus, or T-cells, and are nude immunodeficient models.

CD57BL/6

This laboratory mouse strain was the 2nd mammalian species to ever have its genome published in entirety. They originate from the Bussey Institute for Research in Applied Biology in 1921. These mice are often selected for easy breeding and availability of congenic strains. These mice are particularly sensitive to odors, noise, pain, cold, alcohol and morphine addiction.

CB17

CB17 mice are of a congenic strain that carry the immunoglobulin heavy chain allele (Igh-1b) from a C57BL/Ka on a BALB/c background. They are an ideal control for the CB17/SCID immunodeficient mouse model

NSG

Also known as NOD scid gamma, these mice are deficient in NK, T and B cells as well as multiple cytokine pathways. They also have reduced dendritic cell function and defective macrophage activity and lack a complement system. They are one of the most immunodeficient models available and unlike NOD/SCID mice, NSG mice do not develop thymic lymphomas and can be used for long-term experiments.

Swiss Nude

These mice originate from the 1974 Gustave Roussy Institute (Villejuif, France) Swiss stock. They are T cell deficient, nude and albino.

All laboratory studies are performed by experienced personnel in a GLP-compliant and IACUC-regulated facility in Austin, Texas. Please contact us at info@altogenlabs.com, or call 512-433-6177 to discuss xenograft study details.