Paper - Review

DOI: 10.1136/jitc-2021-002531

Abstract

Background

Neoantigen (NeoAg) peptides
← displayed at tumor cell surface ← by human leukocyte antigen molecule
→ show exquisite (tumor specificity)
→ can elicit T-cell mediate tumor rejection

❓: few NeoAgs
→ are predicted → to be shared between patients

❓: None ← to date
→ have demonstrated therapeutic value
← in the context of vaccination

Methods

A phase I trial ← of personalized NeoAg peptide vaccination (PPV)
← of 24 stage III/IV NSCLC patients
← who had previously progressed following multiple conventional therapies
← including 1⃣ surgery 2⃣ radiation 3⃣ chemotherapy 4⃣ tyrosine kinase inhibitors (TKIs)

❗: Primary endpoints ← of the trial
→ evaluated → 1⃣ feasibility 2⃣ tolerability 3⃣ safety of the personalized vaccinations approach
❗: Secondary trial endpoints
→ assessed → tumor-specific 1⃣ immune reactivity 2⃣ clinical responses

9 → continued TKI therapy
← concurrent with PPV
7 → received PPV alone
∵ of the 16 patient with EGFR mutations

Results

24 → were immunized
← with personalized NeoAg peptides
∵ out of 29 patients ← enrolled in the trial

Median 1⃣ PFS 2⃣ OS
← of the 24 vaccinated patients
→ were 1⃣ 6.0 2⃣ 8.9 months

7 RECIST-based objective clinical responses
← including one complete response
→ were observed
← within 3-4 months ← following initiation of PPV

❗: all 7 clinical responders
→ had EGFR-mutated tumors
‼: including 4 patients
→ had continued TKI therapy ← concurrently with PPV

5 of 7 responding patients
→ demonstrated vaccine-induced T-cell responses
→ against EGFR NeoAG peptides
∵ Immune monitoring

2 highly shared EGFR mutations
← 1⃣ L858R 2⃣ T790M
→ were shown → to be immunogenic
← in four of the responding patients
∴ Increases ← in peripheral blood neoantigen-specific CD8+ T-cell frequencies
← during the course of PPV

Conclusion

❗: Personalized NeoAg vaccination
→ is feasible & safe
→ for advanced-stage NSCLC patients

EGFR mutations
→ constitute → shared & immunogenic neoantigens
← with promising immuno-therapeutic potential
→ for large subsets for NSCLC patients

PPV
← with concurrent EGFR inhibitor therapy
→ was well tolerated
→ may have contributed → to the induction of PPV-induced T-cell responses

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