LBA6 - UCPVax therapeutic vaccination promotes cytotoxic and Th1 polarized antitumor CD4 T cells and epitope spreading in patients with advanced non-small cell lung cancer

Background

The stimulation of antitumor CD4 T helper response represents a critical requirement for therapeutic cancer vaccine effectiveness. In this context, we developed a Th1-inducer anticancer peptide vaccine derived from telomerase called UCPVax (Dosset et al. Clin Can Res 2012). The safety and efficacy of UCPVax therapeutic vaccination were recently reported in metastatic non-small cell lung cancer (NSCLC) phase I/II trial (Adotévi et al., J Clin Oncol 2022, NCT02818426). Here, we described the immunological responses promoted by UCPVax.

Methods

Immune monitoring was performed in 52 patients with refractory metastatic NSCLC previously vaccinated with three doses of UCPVax for six times (one per week) followed by boost every two months for one year. Blood samples were collected before and at different times after vaccination. Vaccine-specific CD4 T cell responses and epitope spreading were evaluated by IFN-γ ELISPOT assay. MHC class II pentamer staining and intracellular cytokine secretion assay were used for the assessment of phenotype function and polarization of antigen specific CD4 T cells. Vaccine induced antibody response was measured by ELISA.

Results

Seventy % of patients mounted strong UCP-specific CD4 T cells after vaccination regardless the dose level. UCPVax induced de novo and strong UCP-specific CD4 T-cell response and the intensity of the response increased according to the number of vaccinations. The UCP-specific CD4 T cells were effector memory phenotype, showed cytotoxic potential and (IFN-γ,TNF-a, IL-2)⁺ Th1 polarization which were maintained in long-term responders. Increased level of antibody response against UCP was found in 45% of patients which was correlated to the number of UCP-CD4 T cells. Furthermore, UCPVax induced epitope spread responses against various tumor antigens in most of patients analyzed. Finally, patients displayed polyfunctional anti-UCP CD4 response and epitope spreading had a better survival.

Conclusions

UCPVax vaccination promotes highly functional and long-lasting tumor specific CD4 T cell responses associated with the improvement of patients’ survival.

Clinical trial identification

NCT02818426.

Legal entity responsible for the study

O. Adotevi.

Funding

National Cancer Institute INCa France PHRC program.

Disclosure

O. Adotevi: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Personal, Principal Investigator: MSD. V. Westeel: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Amgen, Lilly, MSD, BMS. C. Borg: Financial Interests, Personal, Advisory Role: MSD Oncology, Roche; Financial Interests, Institutional, Sponsor/Funding: Bayer. All other authors have declared no conflicts of interest.