Featured study: Mimicking a tumor in a chip to study new lung cancer therapies

Small cell lung carcinoma:
Tackling a resistant cancer

AIM Biotech’s organ-on-a-chip has again demonstrated again how its technology allows the simulation of a tumor to study the migration of T cells in a human tumor environment.

Mahadevan and coll. studied a possible new therapy to treat small cell lung carcinoma. This type of cancer is particularly resistant to natural immunogenicity, meaning that the immune system is not able to recognize the tumor cells as a danger to the organ. This characteristic makes this cancer hard to treat with conventional therapies.

 

The scientists explain in this study that small cell lung carcinomas are composed by different types of cells. The tumors can contain cells expressing low or high levels of MHC I, an important protein complex that confers immunogenicity. They found that patients with higher levels of MCH I in the cancer cells responded better to therapy. Therefore, the authors hypothesized that tumor cells expressing MHC I would allow the detection of the tumor by the innate immune system, making them easier to treat with conventional cancer therapies.

Emulating 3D tumors in the lab on AIM’s organ-on-a-chip

They took advantage of AIM Biotech’s organ-on-a-chip to create 3D tumors with different compositions: tumors containing only cancer cells expressing high levels of MHC I, and tumors with a mix of cells expressing high or low content of MHC I. They grew both types of tumor spheroids and injected them into the matrix of the AIM chip to mimic two different types of small cell lung carcinoma. After, they injected T cells into the fluidic channels beside the 3D chamber of the chip and studied its migration into the tumor spheroids. The migration of T cells into the tumor relates with the capability of immunogenicity. They found that even in tumors where only 25% of cells express MCH I, T cells migrate inside the tumor. Most importantly, these in vitro results were then validated by the in vivo animal models. The cancer cells expressing low levels of MHC I successfully evaded the immune response and grew into larger tumors in the host over time. In contrast, the cancer cells expressing high levels of MHC I induced spontaneous rejection by the host and were heavily infiltrated with T cells, similar to the results shown in AIM chips. This discovery marks MHC I as a novel biomarker and suggests that on patients with small cell lung carcinoma that contains only low expression MCH I cancer cells, new immunotherapeutic approaches such as epigenetic inhibitors should be considered.

This study proposes new biomarker and new therapies for the poorly immunogenic small cell lung carcinoma. With AIM technology, the assay on the 3D chip recapitulates the immune cell infiltration process that occurs in vivo in an organ, bringing it on a simple bench assay.

Gathering more predictive, human-relevant data like this is what AIM’s unique human-on-a-chip tech is all about. Want to discuss how this researcher-friendly tech can transform your research? Use the chat bubble on the bottom right corner of this page, and we’ll reach out to you—or check out our Contact Us page.

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