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852 Modified-epitope-based vaccine (OSE2101) combined with anti-PD-1/IL-7v bispecific antibody sustains long-lasting tumor specific antigen memory T cell response in vivo
  1. Belarif Lyssia,
  2. Julien Taurelle,
  3. Ariane Desselle,
  4. Justine Durand,
  5. Margaux Seite,
  6. Caroline Mary,
  7. Geraldine Teppaz,
  8. Virginie Thepenier,
  9. Cecile Batty,
  10. Berangere Vasseur,
  11. Thomas Vandewalle,
  12. Laurie Cordonnier,
  13. Aurore Morello and
  14. Nicolas Poirier
  1. OSE Immunotherapeutics, Nantes, France


Background OSE2101 is a cancer vaccine composed of 9 optimized epitopes of 5 different tumor-associated antigens (TAAs) CEA, p53, HER-2/neu, MAGE2, MAGE3 restricted to HLA-A2 combined with a universal helper T cell epitope (PADRE) characterized to induce a helper T lymphocyte (HTL) response. OSE2101 is designed to break self-tolerance and promotes tumor-specific cytotoxic-T lymphocytes (CTLs) against TAAs and Helper T Lymphocyte response. In phase III clinical trial, OSE2101 shown overall survival (OS) improvement compared with Chemotherapy (CT) (HR 0.59; p = 0.017) in patients with Non-Small Cell Lung Cancer after immunotherapy failure (ESMO 2021 #47LBA). At preclinical stage, OSE developed a BICKI®IL7v immunocytokine, anti PD-1 fused to IL7 mutein (IL7v) to reinvigorate PD1+ IL-7R+ tumor-specific T cells and sustain long-term response. IL-7 represents the main homeostatic cytokine, enhancing TCR repertoire diversity and favoring expansion/pro-survival of naïve and memory T cells. In this study, our goal was to evaluate the potential combination of OSE2101 and anti-PD-1/IL-7v to enhance frequency of anti-TAA tumor-specific cytotoxic-T lymphocytes.

Methods HLA-A2/DR1 KI mice were treated twice by OSE2101 injections (subcutaneous) +/- anti-PD-1/IL-7v. IFN-γ ELISPOT assay was used to measure CTL response in the spleen and bronchoalveolar-lavage at short (D28) and long-term (D49).

Results Phase II results showed that OSE2101 was able to induce a broad CTL and HTL responses in non-small cell lung cancer patients associated with clinical efficacy. In A2/DR1 transgenic mice, OSE2101 elicited a good CTL immunogenicity response in periphery but also induces lung-resident-memory T cell activation for a direct local anti-tumor efficacy. We next evaluated immunogenicity induced by combining with the Anti-PD-1/IL7v.

Anti PD-1/IL7v monotherapy efficiently antagonizes PD-1 receptor (pSHP-1) and CIS-delivers IL-7 cytokine to cis-potentiate PD-1+ tumor-specific T-cells. The bifunctional compound significantly sustains survival and proliferation of non-exhausted TCF1+ stem-like-memory T cells and demonstrated efficient monotherapy efficacy in orthotopic and ectopic mouse models by promoting long-term memory anti-tumor-T-cell response as evaluated by tumor-rechallenge model.

In A2DR1 immunogenicity model, the combination of OSE2101 + anti PD-1/IL7v treatment demonstrates significant higher peripheral, and lung resident tumor-specific-CTL response was observed as measured by IFNγ ex-vivo restimulation in both short-term or long-term models suggesting that Anti-PD-1 IL7v enhances OSE201 efficacy by favoring memory tumor-specific T cell.

Conclusions Our preclinical data support the potential benefit of combining modified-epitope-based Tedopi vaccine OSE2101 and anti-PD-1/IL7v immunocytokine to enhance magnitude and long-term maintenance of clonal anti-tumor-specific T cells.

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