p53 Vaccines vs. Neoantigen Vaccines:
A Systematic and Comparative Review of Tumour Antigen Strategies in Cancer Immunotherapy
First Author/ Presenter: Isaac Leong Chyi Khin
Co-author: Shakthee Sivakumar
1st Year Undergraduate in Medical Biotechnology (BASc)
1st Year Undergraduate in Medicine (MBBS)
NCCM-26-0024
p53 tumour suppressor gene is known as the “guardian of the genome” and plays a critical role in maintaining genomic stability.
p53-targeted vaccines have emerged as a promising approach in cancer immunotherapy, aiming to enhance anti-tumour immune responses.
Neoantigen vaccines target unique, tumour-specific mutations found in individual patients.
A systematic review and comparative synthesis was conducted to evaluate both vaccine strategies. The comparison focused on:
Background & Rationale:
p53 Vaccines vs. Neoantigen Vaccines
Inclusion Criteria
Exclusion Criteria
PRISMA2020 Flow Diagram: Study Identification and Screening
Author & Year | Intervention | Participants | Outcome |
Keskin et al., (2018) | Personalized neoantigen vaccine (up to 20 long peptides + poly-ICLC) | 10 patients enrolled with newly diagnosed MGMT-unmethylated glioblastoma (8 vaccinated; 2 withdrawn due to insufficient neoepitopes/progression). | Median PFS 7.6 months; Median OS 16.8 months. All patients eventually died from progressive disease. |
Li et al., (2020) | Personalized neoantigen peptide-pulsed DC vaccine | 12 patients with heavily treated metastatic lung cancer | ORR 25%, DCR 75%, Median PFS 5.5 months, Median OS 7.9 months. |
Ott et al., (2017) | Personalized neoantigen vaccine (up to 20 long peptides + poly-ICLC), 5 priming + 2 booster doses | 6 vaccinated patients with high-risk melanoma (Stage IIIB/C and IVM1a/b) | 4/6 with Stage IIIB/C had no recurrence at 25 months. 2/6 with Stage IVM1b achieved complete response after subsequent anti-PD-1 therapy. |
Carreno et al., (2015) | Personalized neo-epitope vaccine (dendritic cell-based) | 5 patients with metastatic melanoma | Cumulative rate of metastatic events significantly reduced; sustained PFS. 2/5 had objective vaccine-related responses. 1 had late relapse due to B2M deficiency. 1 had complete response with PD-1 blockade. |
Author & Year | Intervention | Participants | Outcome |
Hardwick et al., (2014) | p53MVA at 1.0 × 10⁸ or 5.6 × 10⁸ pfu | 12 patients with refractory gastrointestinal cancers. | Grade 2 adverse events; enhanced p53-specific CD8⁺ T-cell responses (P = 0.03); |
Chiappori et al., (2019) | Wild-type TP53–transfected dendritic cell vaccine ± all-trans-retinoic acid | 69 patients with extensive-stage small cell lung cancer (SCLC) after chemotherapy. | Positive immune responses occurred in 20% (Arm B) and 43.3% (Arm C); ORR to second-line chemotherapy was 15.4% (Arm A) and 16.7% (Arm B) |
Schuler PJ et al., (2014) | Adjuvant dendritic cell (DC) vaccine | 16 patients with head and neck squamous cell carcinoma | 69% (11/16) showed increased p53-specific T-cell responses |
Blakemore et al. , (2020) | Targeted resequencing of 22 genes in CLL4 trial samples | 499 patients with chronic lymphocytic leukaemia | Demonstrated that TP53, biallelic BIRC3, and MAPK-ERK pathway mutations were associated with poorer progression-free and/or overall survival. |
p53-targeted Vaccines Clinical Trials:
Neoantigen-based Vaccines Clinical Trials:
Sample of Clinical Trial Outcomes:
p53 Vaccines vs. Neoantigen Vaccines
Both approaches were well tolerated and capable of inducing antigen-specific immunity. However, neoantigen vaccines exhibited greater immunogenicity, superior clinical outcomes, and stronger evidence of durable anti-tumour efficacy compared to p53-targeted vaccine.
Conclusion:
Thank You
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