Cutting edge tools for lung cancer research and drug discovery

In vivo murine CMT models from lung carcinoma cell lines

The CMT 64, 64/61, 167 and 170 cell lines from mouse alveolar lung carcinoma are widely used to investigate metastasis, immune responses, and immunoresistance. Specifically, the CMT 64 cell line serves as an in vivo tumourigenesis system, known for its stable growth and consistent morphology both in culture and in lung metastases following subcutaneous inoculation. Building on this model, the CMT 167 line was selected for its enhanced metastatic potential, making it valuable for investigating metastatic mechanisms.

Murine lung cancer lines to study RAS biology

Murine Lewis lung carcinoma engineered 3LL NRAS KO cell lines, which have the NRAS gene knocked out, show increased dependence on oncogenic KRAS-G12C. These cell lines are useful models for studying the effects of KRAS-G12C inhibition on the tumour microenvironment and anti-tumour immunity.

KPAR cell lines, developed from tumours in an immunogenic syngeneic transplantation model of KRAS-mutant lung adenocarcinoma, replicate the mutational signature of human lung cancer. These cell lines are responsive to immunotherapy, making them valuable for investigating combined targeted and immunotherapy approaches.

Image: Combination of KRAS-G12C inhibitor with IGF1R plus mTOR inhibitors increases in vivo efficacy. Image adopted from PMID: 31534020, Fig.7 C-H.

Popular human lung cancer cell lines

The A549 and NCI-H460 cell lines are extensively used in cancer and toxicology research. Our collection includes genetically modified A549 lines with knockouts of key lung cancer genes like LIDM1, as well as reporter lines for both A549 and NCI-H460.

We also offer a cisplatin-resistant A549 CisR line for studying resistance mechanisms in lung cancer.

Additionally, our lung squamous cell carcinoma Calu lines are widely applied in cancer research, toxicology, high-throughput screening, and 3D cell culture studies.

Image: Dose–response curve of PF-477736, a selective inhibitor of LIMD1-deficient cells, in A549 isogenic LIMD1−/− line. Image adopted from PMID: 34764236, Fig.1E.

Plasmax™: a physiologically relevant cell culture medium 

Plasmax is a defined cell culture medium that provides a physiologically relevant environment by mirroring the concentration of over 50 components found in human plasma. This media been used to successfully culture the human lung cancer A549 cell line, leading to enhanced sensitivity to inhibitors of fatty acid catabolism and mitochondrial complex II without affecting mitochondrial turnover².

In vivo murine CMT models from lung carcinoma cell lines

The CMT 64, 64/61, 167, and 170 cell lines, as noted earlier, can be used as efficient in vivo models with consistent growth and morphology in both culture and lung metastases. They can also be used in drug discovery for assessing efficacy on metastasis and immunoresistance.

Image: CMT 64 cell line. Image courtesy of the European Collection of Authenticated Cell Cultures (ECACC).

Murine lung cancer lines to study RAS biology

The murine Lewis lung carcinoma engineered 3LL NRAS KO cell lines, as previously mentioned, display increased reliance on oncogenic KRAS-G12C, making them effective models to study KRAS-G12C inhibition in drug discovery. They are particularly useful for developing combination therapies aimed at maximising the efficacy of KRAS-G12C inhibitors in lung cancer.

As described earlier, KPAR cell lines are an immunogenic syngeneic transplantation model of KRAS-mutant lung adenocarcinoma responsive to immunotherapy. As immunocompetent models, they provide an invaluable resource for testing targeted therapies and offer a powerful platform for testing combined targeted and immunotherapy approaches in immune-responsive lung cancer.

Image: Combination of KRAS-G12C inhibitor with IGF1R plus mTOR inhibitors increases in vivo efficacy. Image adopted from PMID: 31534020, Fig.7 C-H.

Cisplatin-resistant A549 cell line

Our cisplatin-resistant lung carcinoma A549 CisR cell line is a valuable model for developing novel predictive biomarkers for therapy response. This line can also be used to gain an improved understanding of the underlying molecular mechanisms of resistance, supporting new drug discovery.

Image: Parent (PT) and cisplatin resistant (CisR) A549 cell lines were treated with increasing concentrations of cisplatin for 72 h. While cisplatin inhibited the growth of both PT and CisR cell lines, the inhibitory effect of cisplatin was greatly reduced in CisR cells relative to parent cells. Image adopted from PMID: 23349823, Fig.3

Patient-derived organoid (PDO) models

Panel of 18 lung cancer organoids derived from Japanese patients, that faithfully preserve the pathology, genetic, and drug response characteristics of the in vivo source patient tumours. These complex 3D in vitro models can support the accurate preclinical evaluation of lung cancer drugs and immunotherapies, under more clinically relevant conditions than traditional cell line models.

Image: Immunofluorescent image of lung cancer organoid, RLUN021 showing epidermal growth factor receptor (EGFR) positive cells following staining with the therapeutic Cetuximab antibody, an anti-EGFR monoclonal antibody. This image has been provided by the group of Professor Motoki Takagi, Medical-Industrial Translational Center, Fukushima Medical University, Japan.

Patient-derived xenograft (PDX) models

PDX models are created by transplanting human tumour tissue into immunodeficient mice. Our collection of NSCLC PDX models have been developed from multiple regions of primary tumours from patients enrolled in the Lung TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study. PDX models are highly valuable in recapitulating patient tumour characteristics. These include more representative intratumour heterogeneity, genomic features, metastatic patterns and drug responses than traditional cell lines and animal models. These highly translatable models can be used to support accurate preclinical in vivo drug validation.

Image: Schematic illustrating the establishment of PDX models by grafting tumour tissues from a patient into immunodeficient mice, created with Biorender.

Tumour immunology

Our diverse immune checkpoint antibody collection targets proteins crucial for cancer immunotherapy, including; scCTLA4, ICOS, CD70, CD27, CD86, CD134, and sCD40. These tools enable detailed investigations of tumour-immune cell interactions.

Image: Immune checkpoint interactions between a T cell and a cancer cell. Created with BioRender.com

Tumour signalling

For molecular driver research, we offer antibodies targeting EGFR, which is frequently mutated in NSCLC and represents a major therapeutic target. Additionally, we have antibodies targeting tumour suppressor genes, including a panel of p53 antibodies (DO-11, DO-12, DO-1, Pab 240 and Pab 246) to enable detection of p53 with a range of epitopes.