Sydney Malawer
Pronouns: she/her
Research Mentor(s): Marisa Aikins
Research Mentor School/College/Department: Internal Medicine / Medicine
Program:
Authors: Sydney Malawer, Marisa Aikins, Sofia Merajver
Session: Session 6 3:40-4:30 p.m. Hussey Room
Poster:
Abstract
ALK+ non-small cell lung cancer (ALK+ NSCLC), making up 5-6 % of all lung cancers, is driven by the rearrangement of the Anaplastic Lymphoma Kinase (ALK) gene with the EML4 gene, which induces the transformation of lung cells resulting in constitutive activation of ALK. Current treatments include three generations of ALK tyrosine kinase inhibitors, where first-line and last-line treatment are alectinib and lorlatinib TKIs, respectively. Currently, there are limited options to investigate the tumor immune microenvironment (TIME) and lymphoid organs in ALK+ NSCLC. One option is via an intratracheal instillation of an adenoviral system used to induce the oncogenic eml4-alk rearrangement in a mouse lung. However, the timeline for this model is on the order of months and it is difficult to harvest tumor spread throughout the mouse lung tissue to study the TIME. Therefore, three cell lines (EA1, EA2, EA3) developed from this semi-de novo model were acquired to study the TIME with a shorter timeline and that can be grown in multiple settings (e.g. subcutaneous, intravenous, orthotopic, etc.). This study focuses on the validation of these cell lines in vitro and in vivo utilizing three TKIs, alectinib, lorlatinib, and gilteritinib, and one immune checkpoint inhibitor, anti-PD-1. All three cell lines were sensitive to TKIs in vitro, inhibiting cell growth, while anti-PD-1 supported cancer cell growth. When these cancer cells were co-cultured with splenocytes from naïve, immune-competent mice, there was greater inhibition of cancer growth, suggesting the cancer cells are reactive to immune populations as well. Finally, the cell lines were further validated in vivo where steady tumor growth was observed and sensitivity to the TKIs remained. Thus, a tumor-static effect, one of the key hallmarks of ALK+ NSCLC was validated. As a result, these cell lines were observed to be an acceptable alternative to study the immune environment in ALK+ NSCLC on a faster timescale.
