演題：Development and Design of Personalized Vaccines for the Treatment of Advanced Non Small-Cell Lung Cancer

演者：Gregory A. Lizee 博士（Department of Immunology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center）

抄録：Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen (HLA) molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination. We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies.  Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the immunization approach, and secondary trial endpoints assessed vaccine-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone. Aside from mild transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3–4 months following initiation of PPV, seven RECIST-based objective clinical responses including one complete response were observed. Notably, all seven clinical responders had EGFR-mutated tumors, including four patients that had continued TKI therapy concurrently with PPV. Immune monitoring showed that five of the seven responding patients demonstrated vaccine-induced T cell responses against EGFR NeoAg peptides. Furthermore, two highly shared EGFR mutations (L858R and T790M) were shown to be immunogenic in four of the responding patients, all of whom demonstrated increases in peripheral blood neoantigen-specific CD8+ T cell frequencies during the course of PPV. These results show that personalized NeoAg vaccination is feasible and safe for advanced-stage NSCLC patients. The clinical and immune responses observed following PPV suggest that EGFR mutations constitute shared, immunogenic neoantigens with promising immunotherapeutic potential for large subsets of NSCLC patients. Furthermore, PPV combined with EGFR inhibitor therapy was well-tolerated and may have contributed to the induction of PPV-induced T cell responses.

日時：2024年6月18日（火）16：00 〜 17：00

場所：セミナー室B

連絡先：片山　量平（内線 5421）

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