Cancer Cell: BioNTech new paper - tumor neoantigen vaccine + chemotherapy + PD-1, a three-pronged approach to treat lung cancer

The incidence of cancer is also increasing with the increase in average human lifespan, changes in lifestyle and the increase in pollutants

According to the World Health Organization's International Agency for Research on Cancer (IARC), there will be 9.

In China, both the incidence and death of lung cancer rank first among malignant tumors

On August 25, 2022, BioNTech, in collaboration with researchers from Harvard Medical School, Washington University in St.

The study reports a phase 1b clinical trial combining the individualized neoantigen cancer vaccine NEO-PV-01 with chemotherapy and the anti-PD-1 drug pembrolizumab in metastatic non-squamous non-small cell lung cancer.

Tumor cells generate neoantigens (Neoantigen) through gene mutation, and the neoantigens are presented on the cell surface through MHC molecules, which are subsequently recognized by T cells

However, with the rapid development of sequencing and bioinformatics technology, scientists can rapidly identify candidate neoantigens in individual patients through specific algorithms, and design personalized neoantigen vaccines accordingly

In this latest study, the research team reports data from a Phase 1b clinical trial combining the personalized vaccine NEO-PV-01 with chemotherapy and pembrolizumab in the first-line treatment of metastatic non-squamous NSCLC treatment

Figure 1: Clinical study design of personalized neoantigen vaccine NEO-PV-01

The trial is designed to allow patients to receive standard-of-care treatment, which is four cycles of chemotherapy in combination with pembrolizumab, during vaccine production

Figure 2: Flow chart of Phase 1b clinical trial of personalized neoantigen vaccine NEO-PV-01

In the ITT arm, 16 patients completed vaccination and only minor related adverse events were reported, indicating that the combination of NEO-PV-01 with chemotherapy and pembrolizumab was safe and well tolerated

Figure 3: Response rate and durability after NEO-PV-01 combined with chemotherapy and pembrolizumab

The research team performed detailed molecular and immune analyses of the tumor microenvironment (TME) and peripheral blood of these patients, and they found that neoantigen vaccination in combination with chemotherapy and anti-PD-1 had a strong synergistic effect

Figure 4: Correlations with clinical response observed in the tumor microenvironment (TME), including T cell infiltration, MHC class II expression, and TCR diversity

More interestingly, the research team observed epitope spread responses to common driver mutations KRAS G12C and G12V in multiple patients, with three-quarters of epitope spread to KRAS-mutated patients achieved at least 9 months after treatment initiation.

Furthermore, single-cell sequencing of neoantigen-specific CD4+ T cells suggested an effector cytotoxic phenotype consistent with a potential role of vaccine-induced CD4+ T cells in mediating tumor cell killing

Figure 5: NEO-PV-01 in combination with chemotherapy and pembrolizumab induces epitope spreading responses in the majority of patients analyzed

Although this study demonstrates the safety and feasibility of NEO-PV-01 in combination with chemotherapy and pembrolizumab as first-line treatment for non-small cell lung cancer, several challenges remain at this stage:

1) Nearly half of the patients were unable to produce vaccines due to low numbers of tumor cells in biopsies or insufficient predicted high-quality neoantigens

2) Some neoantigens are too hydrophobic to be synthesized as long peptides

3) Difficulty predicting the processing of candidate epitopes, which may not be processed and presented on the cell surface

4) The T cell responses induced by neoantigen vaccines tended to be CD4 responses, but were unable to induce strong CD8+ T cell responses
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Research Pattern Diagram

In conclusion, this latest study demonstrates the safety and immunogenicity of the individualized neoantigen vaccine NEO-PV-01 in combination with chemotherapy and pembrolizumab in advanced non-squamous non-small cell lung cancer.
The anti-tumor efficacy still needs to be further verified
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Original source:

Mark M.
Awad, et al.
Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer.
Cancer Cell, 2022.