Featured study: modeling the human tumor microenvironment for IL-15 on AIM technology

IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy

Our applications development manager Lim Sei Hien discusses one recent study in cancer immunotherapy that benefited from the humanized technology in AIM Biotech’s organ-on-a-chip.

The NY-ESO-1 antigen in immunotherapy

NY-ESO-1, or New York esophageal squamous cell carcinoma-1, belongs to the cancer testis antigen (CTA) family. NY-ESO-1 has been an interesting target for immunotherapy, as its expression is mainly restricted to germ cells at fetal level in healthy individuals and it is re-expressed in approximately 75% of cancer patients. Therefore, the therapeutic approach that targets NY-ESO-1 is generally well-tolerated with minimum off-target toxicity. In addition, NY-ESO-1 also elicits humoral and cellular immune responses, which makes it an ideal target for immunotherapy.

Kohli et al. has utilised endogenous T cells (ETC) technology to isolate and expand the patients’ NY-ESO-1-specific T cells ex vivo, and then re-infused them into patients with synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) in a phase I adoptive cellular therapy (ACT) clinical trial. Although the treatment was well-tolerated and the patients responded to the ACT initially, the disease progressed ultimately in all patients.

Based on the data collected from resected tumors, the authors confirmed that NY-ESO-1-specific T cells infiltrated into tumor sites and the tumors also expressed NY-ESO-1-specific antigen. However, the persisting NY-ESO-specific T cells showed decreased proliferation. The authors hypothesized that the decreased proliferation of NY-ESO-specific T cells can be rescued by exogenous IL-15 treatment.

Using AIM technology to test the IL-15 treatment in a human cell environment

They isolated the transferred cells from the patients’ PBMCs and expanded the cells again ex vivo. With the addition of IL-15, the isolated cells expanded much faster as compared to the control group. Most importantly, using AIM Biotech 3D cell culture technology, the cells treated with IL-15 showed a greater than two-fold improvement in targeting and killing tumor cells in a T cell killing assay. In this assay, T cells must pass through an endothelial monolayer to reach and kill the cancer cells on the basal side. This AIM-powered assay faithfully recapitulates the immune cell infiltration process in vivo. These results were consistent across the patient cohorts from different treatment centres. With this, the authors confirmed the effectiveness of IL-15 treatment in reversing the phenotypes of low proliferative NY-ESO-1-specific T cells and presented a new opportunity to combine ACT with approaches to achieve sustained levels of IL-15 in patients.

Gathering more predictive, human-relevant data like this is what AIM’s unique human-on-a-chip tech is all about. Sounds interesting? Check out the links below to learn how our technology and services can benefit your lab, too.

*IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy. Kohli K, Yao L, Nowicki TS, Zhang S, Black RG, Schroeder BA … Pollack SM , J Immunother Cancer. 2021 May;9(5):e002232. doi: 10.1136/jitc-2020-002232.

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