Revealing the Genetic Drivers of Highly Polyfunctional CAR-T Cells for Improved Clinical Outcomes with IsoPlexis’ Duomic

As cancer therapeutics become more personalized, cell therapies have shown great promise. Recent advancements in cell therapies, such as CAR-T therapies, have helped improve clinical outcomes for patients with hard-to-treat cancers. Despite progress being made in the field, patients undergoing CAR-T therapy may still experience disease progression, prompting an urgent need for novel strategies to speed up therapeutic development timelines and predict patient response.

Duomic Detects Proteomic and Transcriptomic Data Simultaneously to Drive the Development of Next-Generation CAR-T Therapies

IsoPlexis’ single-cell functional proteomics has addressed this challenge by characterizing the function of each immune cell. Highly functionally active cells, also known as “superhero” cells, orchestrate the immune response and have been associated with improved clinical outcomes. The presence of these superhero CAR-T products is a key predictor of early and persistent response, as published in multiple peer-reviewed studies.

Now, with IsoPlexis’ Duomic platform, researchers can connect the genes and genetic pathways driving these highly multifunctional “Superhero” CAR-T cells to unlock a new layer of multi-omic resolution for improved predictions. Duomic’s ability to unlock both single-cell sequencing and functional proteomics simultaneously from the same single cell allows researchers to identify the genes driving the overall polyfunctional response to develop better, targeted CAR-T therapies.

IsoPlexis’ Duomic unlocks CAR-T functional multi-omic biology (presented at SITC)

Duomic is an application of functional single-cell analysis and involves integrating direct in vivo proteomic activity from cells with the gene regulatory networks driving those expression patterns. For the first time, researchers can look at both the transcriptomic and functional proteomic data at the same time to produce a higher resolution understanding of the inner workings of the immune system.

In research presented at the 2021 annual meeting of the Society for Immunotherapy of Cancer (SITC), the Duomic platform was used to simultaneously measure the proteomic and gene expression (mRNA) levels of individual CD8+ CAR-T cells in response to specific antigen simulation. Two distinct populations of cells were identified, one with low polyfunctionality and one with high polyfunctionality. These two subpopulations each had a unique gene expression profile, indicating the possible genes that regulate the polyfunctional protein expression of the cells. By identifying genes associated with polyfunctional response, cell therapies can be tuned to leverage these gene pathways and improve clinical outcome.

Functional Multi-Omics for the Development of Next Generation CAR-T Therapies

While the field of CAR-T therapy has advanced significantly over the years, next-generation technologies are needed to fine tune and develop more robust therapies to benefit patients while improving quality control. Functional single-cell proteomics has made progress towards this goal, helping to overcome the complexities of tumor-immune interactions and providing correlative clinical and preclinical immune biomarkers hidden by traditional methods. The ability to directly measure the function of single cells is critical to predicting therapeutic response, cell therapy quality, and more. Now, with IsoPlexis’ new Duomic platform, researchers can go even further, connecting highly functional superhuman cells to their genetic drivers to advance curative medicine across a range of complex diseases.

Share This Article
Subscribe to Follow the Data

Weekly email to keep you at the forefront of single-cell & multiplexed proteomics.