CDX Model Based Pharmacological Efficacy Studies

Biocytogen performed efficacy studies of multiple CDX models in B-NDG mice, including human solid tumor and hematological tumor cell lines, including lung carcinoma, colorectal adenocarcinoma, colon carcinoma, breast cancer, pancreatic carcinoma, bladder carcinoma, glioblastoma, liver cancer, and various leukemia and lymphoma cell lines. We establish subcutaneous, orthotopic, or metastatic tumor models based on our customer’s requirements. In addition, we provide pharmacodynamic (PD) services in these CDX models.

Established CDX Models

 

  Cell lines Tumor type Cell lines Tumor type
Human solid tumor cell lines NCI-H1975 Lung carcinoma, non-small cell ZR-75-1 Breast ductal carcinoma
HCC827 Lung adenocarcinoma MDA-MB-231 Breast adenocarcinoma
NCI-H520 Lung carcinoma DU4475 Breast carcinoma, triple negative
A549 Lung carcinoma MCF7 Mammary gland, breast adenocarcinoma
NCI-H1781 Lung carcinoma bronchoalveolar 5637 Bladder grade II carcinoma
HCT-8 Colorectal Ileocecal adenocarcinoma A431 Epidermoid carcinoma
HCT-116 Colon carcinoma LN229 Glioblastoma
Colo205 Colorectal adenocarcinoma Miapaca-2 Pancreatic carcinoma
Human blood tumor cell lines

 

Daudi Lymphoma, NAMALWA Burkitt’s lymphoma
KG-1 Leukemia, acute myelogenous (AML) Kasumi-1 Leukemia, acute myeloblastic (AML)
Raji Lymphoma, Burkitt’s SU-DHL-1 Large cell lymphoma, Diffuse histiocytic lymphoma
K562 Leukemia (CML) MV4-11 Peripheral blood biphenotypic B myelomonocytic leukemia

 

CDX Models with Luciferase Labeled Cell Lines

 

No. Cell name Cancer type
B-HCL-013 B-luciferase-GFP Raji Cell Line Lymphoma, Burkitt’s
B-MCL-001 B-luciferase-GFP HT-29 Cell Line Colorectal adenocarcinoma
B-MCL-002 B-luciferase-GFP H-1975 Cell Line Lung carcinoma, non-small cell
B-HCL-014 B-luciferase K562 Cell Line Leukemia (CML)
B-HCL-015 B-luciferase MIA PaCa-2 Cell Line Pancreatic carcinoma
B-HCL-010 B-luciferase U-87MG cell line  Glioblastoma

 

Tumor Growth Kinetics of Selected CDX Mouse Models

Case 1: In vivo imaging of NOD-scid mice at 6, 16 and 28 days after inoculation with HT-29-GFP Luciferase cells.

A) The mouse on the left was injected with 5 x 106 cells. The mouse on the right was injected with 5 x 105 (B) Signal intensity and tumor size graph.

 

Case 2: In vivo imaging of NOD-scid mice at 7, 14 and 21 days after inoculation with 4T1-Luciferase cells

(A) The mouse on the left was injected with 5 x 106 cells; the mice on right was injected with 5 x 105 cells. (B) Signal intensity and tumor size graph.

 

Case 3:Human B cell lymphoma CDX model

Raji cells (5×10⁶) were injected into B-NDG, NOD-scid and BALB/C nude mice. (A) Kaplan-Merier survival curves. (B) Relative body weight change. (C) Percentage of human cells in mouse peripheral blood quantified by q-PCR. (D) Liver tumor nodules. (E) Immunohistochemical staining of livers and spleens.

Example CDX Drug Efficacy Studies

Case 1 

Raji-Fluc cells (5 x 10⁵) were injected into B-NDG mice. Antibody X was administered on specified days. (A) Representative in vivo imaging recorded at different time points to monitor tumor progression. (B) Tumor load (as indicated by luciferase activity) kinetic curves post antibody treatment. Early dosing on day 3 in addition to day 10 resulted in robust tumor growth inhibition. In contrast, a single dose at day 10 had little effect.

 

Case 2 

Humanized B-NDG mice engrafted with human CD34+ HSC were intravenously injected with 5 x 10⁵ Raji-Fluc cells. Five days after Raji-Fluc cells implantation, mice were treated with anti-human PD-1 antibody. (A) Images of tumor load as indicated by luciferase activity. Tumor growth was dramatically inhibited by the human PD-1 antibody at day 7. RC=Raji-Fluc + Control. PDH=Antibody X + Humanized Mice. Naive B-NDG=Untreated Group.

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