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ImmunoPrism in CAR-T

 In Advanced Applications, Cofactor Genomics, Molecular Diagnostics, Q&A

ImmunoPrism in CAR-T

Ian Schillebeeckx, Ph.D.

One therapeutic area of immuno-oncology that has excelled in blood cancers is chimeric antigen receptor (CAR-T) T cells. CAR-T is a therapy which uses a patient’s own cells to attack cancer. Briefly, this is done by harvesting a patient’s T cells, genetically engineering those T cells to produce a receptor to a specific antigen, and reintroducing these engineered T cells back into the patient. To outsiders, this approach may seem like science-fiction, however, the therapy has very real and very impressive results in a blood cancer: ~80% of patients have had total remission.

ImmunoPrism is a unique assay which robustly measures the relative abundance of different immune cells. This assay was optimized for solid tumors, especially FFPE archival samples. However, the underlying Immune Health Expression Models that power ImmunoPrism™ were created from primary PBMC samples. Therefore, ImmunoPrism™ is well suited to also studying the immune response in blood based cancers.

CAR-T therapies are being optimized and tested in other indications. In these studies, researchers have active questions that ImmunoPrism™ can help answer:

“What is the product being administered to patients?”

Researchers have found that the ratio of CD4 and CD8 cells administered can alter efficacy. ImmunoPrism can accurately determine the ratio of CD4 and CD8 in CAR-T products. This allows researchers to explore what is most efficacious as well as ensure consistent dosages across patients.

“What is the state of the patient’s immune system prior to transplant?”

Before administration of CAR-T, often patients immune systems are depleted via chemotherapy. This ensures that the engineered T cells can proliferate without competition or inhibition from other immune cells.

“How does the patient’s immune system recover?”

After therapy administration, a patient’s immune system will recover. Different factors control this including the eradication (hopefully) of the cancer itself, the proliferation of engineered T cells, and the recovery of other immune cell types. The recovery, or lack of recovery, can be indicative of a full response, or a patient who may relapse. ImmunoPrism™ profiles 8 of the major cell types in order to give a complete picture of the immune system and help researchers understand how all immune cells change over the course of the therapy.

Traditionally, flow cytometry has been used to measure the presence of immune cells in blood. However, this technology has some practical limitations that makes ImmunoPrism™ better suited:

  1. Flow cytometry (flow) involves calibration of individual machines. In trials with multiple trial sites, this prevents researchers from comparing immune cell measurements across the whole patient cohort. ImmunoPrism™ comes in a kit that has been validated in our CAP certified laboratory to be highly reproducible.
  2. For flow, the less abundant a cell type of interest is, the more starting material is needed to properly measure it. As any other trial, patient samples are finite. The more sample is used for flow, the less is used for other assays asking different, valuable questions. ImmunoPrism™ does not face this challenge because it requires 20ng of RNA (about 100k cells) and has limits of detection as low as 0.04%.
  3. Not all cell types have recognized flow markers. Therefore, flow is not able to profile the abundance of some immune cells, such as macrophages. Since ImmunoPrism™ is based on RNA, it does not have this limitation. The ImmunoPrism™ assay is able to discern even subtle immune changes, such as quantification of M1 and M2 polarized macrophages.

In CAR-T therapy studies, researchers study the host immune system and response, as well as the engineering cells, themselves. ImmunoPrism™ is well positioned to measure these aspects and overcome the practical challenges of flow cytometry. Given this, we believe that ImmunoPrism™ can help guide the future of CAR-T research, improving efficacy and helping CAR-T move to other indications.

Contact us to share more about your CAR-T studies, and learn how ImmunoPrism™ can accelerate your translational work.

 

Note: Cofactor’s ImmunoPrism™ Assay is offered both for Research Use Only (not to be used as a diagnostic assay) and as a CAP-validated assay. Please contact us to discuss which option is right for your application.

 

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482931/
  2. https://www.nejm.org/doi/pdf/10.1056/NEJMoa1709866
  3. https://www.ncbi.nlm.nih.gov/pubmed/26369987
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