Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 1;13(7):1658.
doi: 10.3390/cancers13071658.

Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC

Ioannis S Pateras  1 , Athanasios Kotsakis  2 , Margaritis Avgeris  3   4 , Evangelia Baliou  5 , Panagiotis Kouroupakis  6 , Eleni Patsea  7 , Vassilis Georgoulias  8 , Jeanne Menez-Jamet  9 , Jean-Pierre Kinet  9   10 , Kostas Kosmatopoulos  9
Affiliations

Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC

Ioannis S Pateras et al. Cancers (Basel). .

Abstract

Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors.

Methods: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low.

Findings: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219-0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131-0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11-0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278-0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy.

Conclusions: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors.

Keywords: Vx-001; cancer vaccines; granzyme B; immunologically cold tumors; metastatic non-small cell lung cancer; tumor-infiltrating lymphocytes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. J.M.-J. is an employee and shareholder of Vaxon Biotech. K.K. and J.P.K. are shareholders of Vaxon Biotech. All remaining authors have nothing to disclose.

Figures

Figure 1
Figure 1
High-tumor-infiltrating lymphocyte (TIL) and low-TIL infiltrate. Representative photos with high and low CD3, CD8 and granzyme B (GZMB) infiltrate in two non-small cell lung cancer (NSCLC) patients. Arrowheads depict positive immunostaining. Scale bar: 100 μm.
Figure 2
Figure 2
Overall survival (OS) in patients with PD-L1(-), tumor-associated immune cell (TAIC) low, CD3-TIL low and CD8-TIL low tumors. OS was measured in patients with PD-L1(-) (A), TAIC low (B), CD3-TIL low (C) and CD8-TIL low (D) tumors.
Figure 3
Figure 3
Time to treatment failure (TTF) in patients with PD-L1(-), TAIC low, CD3-TIL low and CD8-TIL low tumors. TTF was measured in patients with PD-L1(-) (A), TAIC low (B), CD3-TIL low (C) and CD8-TIL low (D) tumors.
Figure 4
Figure 4
OS and TTF in patients with GZMB-TIL low tumors. OS (A) and TTF (B) were measured in patients with GZMB-TIL low tumors.
See this image and copyright information in PMC

References

    1. Moudgil K.D., Sercarz E.E. The T cell repertoire against cryptic self-determinants and its involvement in autoimmunity and cancer. Clin. Immunol. Immunopathol. 1994;73:283–289. doi: 10.1006/clin.1994.1200. - DOI - PubMed
    1. Cibotti R., Kanellopoulos J.M., Cabaniols J.P., Halle-Panenko O., Kosmatopoulos K., Sercarz E., Kourilsky P. Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants. Proc. Natl. Acad. Sci. USA. 1992;89:416–420. doi: 10.1073/pnas.89.1.416. - DOI - PMC - PubMed
    1. Gross D.A., Graff-Dubois S., Opolon P., Cornet S., Alves P., Bennaceur-Griscelli A., Faure O., Guillaume P., Firat H., Chouaib S., et al. High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy. J. Clin. Investig. 2004;113:425–433. doi: 10.1172/JCI200419418. - DOI - PMC - PubMed
    1. Scardino A., Gross D.A., Alves P., Schultze J.L., Graff-Dubois S., Faure O., Tourdot S., Chouaib S., Nadler L.M., Lemonnier F.A., et al. HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy. J. Immunol. 2002;168:5900–5906. doi: 10.4049/jimmunol.168.11.5900. - DOI - PubMed
    1. Vetsika E.K., Konsolakis G., Aggouraki D., Kotsakis A., Papadimitraki E., Christou S., Menez-Jamet J., Kosmatopoulos K., Georgoulias V., Mavroudis D. Immunological responses in cancer patients after vaccination with the therapeutic telomerase-specific vaccine Vx-001. Cancer immunol. Immunotherapy. 2012;61:157–168. - PMC - PubMed