Clinical outcome of patients with various advanced cancer types vaccinated with an optimized cryptic human telomerase reverse transcriptase (TERT) peptide: results of an expanded phase II study.

Abstract

BACKGROUND:

TERT (telomerase reverse transcriptase) plays a critical role in tumor cell growth and survival. In an expanded phase II study, we evaluated the immunological and clinical responses to the TERT-targeting Vx-001 vaccine in patients with advanced solid tumors.

METHODS:

HLA-A*0201-positive patients received two subcutaneous injections of the optimized TERT(572Y) peptide followed by four injections of the native TERT(572) peptide, every 3 weeks. Peptide-specific immune responses were evaluated by enzyme-linked immunosorbent spot at baseline, and after the second and the sixth vaccinations.

RESULTS:

Fifty-five patients were enrolled and 34 (62%) completed the six vaccinations. A TERT-specific T-cell immune response was observed in 55% and 70% of patients after the second and the sixth vaccinations, respectively. The disease control rate (DCR) was 36% [95% confidence interval (CI) 24% to 49%], including one complete and one partial response. Immunologically responding patients had a better clinical outcome than nonresponders [DCR: 44% versus 14% (P = 0.047); progression-free survival (PFS): 5.2 versus 2.2 months (P = 0.0001) and overall survival: 20 versus 10 months (P = 0.041)]. Multivariate analysis revealed that the immunological response was an independent variable associated with increased PFS (hazard ratio = 3.35; 95% CI 1.7-6.7).

CONCLUSION:

Vx-001 vaccine was well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.

• Authors: A Kotsakis, E-K Vetsika, S Christou, D Hatzidaki, N Vardakis, D Aggouraki, G Konsolakis, V Georgoulias, Ch Christophyllakis, P Cordopatis, K Kosmatopoulos, D Mavroudis
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 2 Pg. 442-9 (Feb 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 21873272 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Telomerase
• telomerase reverse transcriptase p572Y, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Cancer Vaccines (administration & dosage, immunology)
• Female
• HLA-A2 Antigen (immunology)
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Neoplasms (immunology, pathology, therapy)
• Telomerase (administration & dosage, immunology)
• Treatment Outcome