In cancer research, selecting the right cell line is vital for producing reliable, translatable results. The success of a study often hinges on using well-characterized, highly cited cell lines that accurately represent the disease being studied. Additionally, many of the leading cell lines used in cancer research are murine cancer cells, which are optimal for transplantation into syngeneic animal models to gain a holistic view of the immune system response to cancer. Kerafast cell lines, sourced directly from academic institutions, provide researchers with trusted tools to explore new cancer therapies.

The following cell lines from Kerafast are key tools in cancer research, each offering unique characteristics that enhance our understanding of specific cancer types and therapeutic approaches.

• MC-38 cells, derived from a colon tumor in C57BL/6 mice, are highly immunogenic and commonly used in studies related to immunotherapy, particularly targeting the PD-1/PD-L1 pathway. Their relevance to human tumor heterogeneity makes them a valuable model in exploring combination therapies.
• KPCY cells are derived from a genetically engineered mouse model of pancreatic ductal adenocarcinoma, harboring mutations in Kras and Trp53 genes. They are instrumental in studying the aggressive nature of pancreatic cancer and the effects of combination therapies, particularly those involving immune checkpoint inhibitors.
• OSCC cell lines, including MOC1, MOC2, and MOC22, are used to study head and neck cancers. MOC2 cells are known for aggressive growth, while MOC1 and MOC22 exhibit slower patterns, making them suitable for various experimental applications, including photoimmunotherapy and engineered NK cell studies.
• HPDE-H6c7 cells represent normal human pancreatic duct epithelial cells and are used as controls in pancreatic cancer research. They help identify differences in protein expression between healthy and cancerous cells, aiding in the discovery of potential therapeutic targets.

Cell Lines Supporting Cancer Research

Recent publications citing Kerafast cell lines cover research topics that include the effect of dietary probiotics on antibody therapy effectiveness, how “fight or flight mode” impacts tumor immunity, and the mechanisms by which pancreatic cancer exploits iron-containing proteins for tumor progression. This research highlights the critical role of selecting the right cell lines to advance our understanding of cancer biology and treatment strategies.

Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment.

MC-38 Cell Line derived from C57BL6 murine colon adenocarcinoma cells.

Immune checkpoint inhibitor (ICI) therapy using monoclonal antibodies can ramp up antitumor immune responses in patients with certain forms of cancer, but more than just the antibody biologic contributes to the effectiveness of ICI. This 2024 study published in Cell explores the effect of the probiotic Lactobacillus reuteri and its metabolites on antitumor immunity and ICI effectiveness in live mouse models. Mice were transplanted with MC-38 adenocarcinoma tumor cells from Kerafast (ENH204-FP). Researchers found that orally administered L. reuteri (Lr) can be found in the tumor microenvironment, and that the presence of Lr promotes antitumor immunity in melanoma.

Further, the Lr-derived metabolite indole-3-aldehyde (I3A) enhances the efficacy of ICIs by interacting with the aryl hydrocarbon receptor (AhR) on CD8 T-cells. This interaction triggers the production and release of inflammatory cytokines, such as IFNγ, which amplify the antitumor immune response. The researchers also found that mice placed on high-tryptophan diets experienced lower tumor growth rates and higher survival rates. Lastly, researchers used stage IV melanoma human patient sera to find that I3A was associated with improved ICI response.

These findings suggest that more than just the immune checkpoint inhibitor therapy contributes to antitumor responses. The association between supplemental probiotics, native microbes, and dietary additions are all necessary for effective immunotherapy for cancer treatment. This study has implications in the holistic treatment of cancer to improve health outcomes. Additionally, the use of the highly cited MC-38 cell line highlights its effectiveness at creating tumor microenvironments in live animal models to further this kind of cancer research on the pathway to clinical trials.

Adrenergic receptor signaling regulates the CD40-receptor mediated anti-tumor immunity.

Some cancer cells are non-immunogenic, or “cold”, meaning they do not garner the attention of anti-tumor immune cells and are left to replicate unchecked. Anti-CD40 antibodies can help increase the immunogenicity of a tumor by activating dendritic cells (DCs) which flag down cytotoxic T-cells, but the results of anti-CD40 in immunotherapy trials have fallen short. A possible factor in the moderate effectiveness of anti-CD40 therapy could be in the role stress plays in patients. Sympathetic nervous system activation (like the release or norepinephrine during “fight or flight mode”) can cause release of anti-inflammatory cytokines and anti-apoptotic pathway activation, further “cooling down” nonimmunogenic tumors.

This 2023 study published in Frontiers of Immunology demonstrates the potential role of the sympathetic nervous system on the effectiveness of anti-CD40 in cold tumor microenvironments. Researchers used the MOC2 oral squamous cell carcinoma mouse cell line transplanted into syngeneic animal models for in vivo studies. They found that stress-related signals in the body, specifically through the activation of a receptor called β2 adrenergic receptor (β2AR) on DCs, can reduce the effectiveness of anti-CD40. This stress signaling interferes with the way CD40 works in the immune cells, weakening the immune response against the tumor.

Interestingly, when researchers added the drug propranolol, which blocks these stress signals, the immune response was much stronger. The combination of propranolol with anti-CD40 led to better tumor shrinkage, more T-cells attacking the tumor, and fewer cells that suppress the immune response. This discovery suggests that combining anti-CD40 with a drug that blocks stress signals could be a more effective way to treat cancers that are otherwise resistant to the immune system. The results also suggest another effect that chronic stress has on patients with cancer, adding to a more comprehensive understanding of how to best improve cancer treatment outcomes.

Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

For oral squamous cell carcinoma in the head and neck, treatment options that conserve tissue are crucial for improving patients’ functional and aesthetic outcomes. Photodynamic therapy (PDT) is a nonsurgical treatment that uses light to activate photosensitive dyes which generate a cell-killing oxygen species. These photosensitizers are taken in more readily by tumor cells than healthy cells, making PDT a specific and promising cancer treatment candidate.

In this 2024 study, researchers evaluated the efficacy of PS nanoparticle-mediated PDT (PS-PDT) in three different OSCC tumor models in vivo: the Cal-33 human cell line, the MOC22 mouse cell line, and the VX-22 rabbit cell line. Researchers found that all tumor models selectively took in the photosensitive dyes, and that PS-PDT was effective in all models, eliminating tumors with minimal side effects and cosmetic effects.

This study adds to the preclinical research surrounding PDT and other therapies for OSCC, one of the most prevalent forms of head and neck cancer in the world. This is yet another example of the importance of highly cited animal cell lines, like the MOC1, MOC2, and MOC22 mouse OSCC cell lines, in understanding new treatment pathways for cancer.

Neutralization of p40 Homodimer and p40 Monomer Leads to Tumor Regression in Patient-Derived Xenograft Mice with Pancreatic Cancer.

H6c7 is an immortalized epithelial cell line derived from normal human pancreatic duct epithelial (HPDE) cells.

Pancreatic cancer is one of the deadliest cancers, with very few treatment options and a low survival rate. It’s hard to catch early because the symptoms are unclear, there aren’t specific tests to detect it, and the cancer grows quickly. As of now, several antibody therapies have been developed or are in various stages of clinical trials for treating pancreatic cancer. However, the number of FDA-approved antibody therapies specifically targeting pancreatic cancer is limited. Some of the key therapeutics include nivolumab and pembrolizumab, which target PD-1.

To understand more potential therapeutic targets, this 2023 Cancers study investigates Interleukin-12 (IL-12), which plays a crucial role in how the immune system fights cancer. They found that in human pancreatic duct epithelial cells HPDE-H6c7 (ECA001-FP) and patient sera, certain forms of IL-12, called p40monomer (p40) and p40 heterodimer (p40₂), were higher than normal, while the forms IL-12 and IL-23 were lower. Cancer cells in the pancreas also produced more of these p40₂ and p40 proteins than healthy cells.

Interestingly, when scientists used antibodies to block p40 and p40₂, the cancer cells started to die, but the healthy cells were not harmed. In experiments with live mouse models, these antibodies also caused the tumors to shrink. This research suggests that targeting these specific proteins could be a new way to treat pancreatic cancer, offering hope for more effective therapies of this deadly disease in the future. Additionally, the research helps further understanding of the proteins complicit in tumor immune system evasion.

NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron-Sulfur Cluster Proteins.

Pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer, relies heavily on a process called autophagy to survive and grow. Autophagy is like a cellular recycling system that breaks down and reuses parts within the cell, which is crucial for the cancer’s ability to keep up with its uncontrolled growth and increased metabolic demands. Because of this, PDAC becomes dependent on autophagy to maintain itself. However, the metabolic materials PDAC needs from autophagy to drive tumor progression is unclear.

One key process in PDAC is the breakdown of ferritin, a protein that stores iron in cells, through a specific type of autophagy called ferritinophagy. This process releases iron that the cancer cells need to continue growing. Using patient samples and murine models grafted with KPCY mouse pancreatic cancer cells (EUP013-FP), researchers in this 2022 Cancer Discovery study found that ferritinophagy is more active in PDAC, helping the tumor access the iron it needs. By blocking ferritinophagy, researchers were able to slow down tumor growth and extend survival, although the cancer might try to find other ways to get iron. High levels of ferritinophagy were also linked to worse outcomes for PDAC patients.

Pancreatic cancer’s reliance on autophagy, particularly ferritinophagy, is essential for its survival and growth. Targeting these processes could offer a new way to treat this aggressive cancer, especially since autophagy’s role can vary depending on the tumor’s stage and environment.

Conclusion

The selection of appropriate cell lines is fundamental to the success of cancer research, enabling the development of more accurate models for studying complex disease mechanisms and therapeutic responses. By using highly cited, well-characterized cell lines sourced from academic institutions, researchers can ensure the reliability and relevance of their findings. These studies not only deepen our understanding of cancer biology but also pave the way for innovative treatment strategies that could lead to improved patient outcomes.

For future immunotherapy studies, this article on selecting the right cell line for cancer antibody research outlines considerations to make when choosing cells for preclinical experiments. Paired with recombinant antibodies optimized for in vivo applications in syngeneic animal models, the right cells and the right antibodies can simulate systemic immune responses to gain a greater understanding of all the factors in antibody-led anti-tumor activity. VivopureX™ antibodies are built off-the-shelf for in vivo applications, and our custom engineering options can create further formats tailor-made for your studies.