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Tumor Biopsy Analysis of Anticancer Vaccine–Treated Patients With Advanced NSCLC

By: Vanessa A. Carter, BS
Posted: Thursday, December 16, 2021

Santiago Viteri, MD, of Instituto Universitario Dexeus and UOMI Cancer Center, Clinica Mi NovAliança, Barcelona, and colleagues analyzed tumor biopsies from patients with non–small cell lung cancer (NSCLC) treated with OSE2101—an anticancer vaccine with HLA-A2–positive restricted modified epitopes targeting tumor-associated antigens such as CEA, HER2, MAGE2, MAGE3, and P53. Data from the ATALANTE-1 trial, which were presented during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 366), showed that all patients expressed HLA class I in their tumors at initial diagnosis.

“Transcriptomic data in the patients that benefited from [OSE2101] showed activated macrophage pathway, high interferon-gamma, and Expanded Immune Gene Signatures scores,” the study authors concluded. “These data will be validated on a larger number of patients treated with [OSE2101] after the step 2 analysis.”

A total of eight HLA-A2–positive tumor biopsies were available from patients with stage IV NSCLC. Primary and secondary resistance to immune checkpoint blockers was observed in three and five participants, respectively. Best responses to OSE2101 included four cases of progressive disease, three of stable disease, and one a partial response. Immunohistochemistry was performed to evaluate HLA-class I, PD-L1, CD8 T cells, HER2, CEA, and P53 tumor expression.

Immunohistochemical analysis uncovered P53 and CEA expression in six and five patients, respectively; P53, CEA, HER2, MAGE2, and MAGE3 were detected in RNA in five tested participants. High CD8 and PD-L1, high CD8 and low PD-L1, and low CD8 and low PD-L1 scores were detected in one, one, and five individuals, respectively. Additionally, one patient who achieved a partial response displayed a high/high immunoscore with a pronounced CD8-positive T-cell tumor infiltration.

In participants who reached stable disease and partial response, between 69% and 97% of tumor cells expressed P53, with this overexpression correlating with activated macrophages. Notably, high Expanded Immune Gene Signature and interferon-gamma scores were reported in individuals who were deemed long-term survivors with secondary immune checkpoint blocker resistance, even after progressive disease.

Disclosure: No disclosure information was provided.



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