Anti-cancer immunotherapy using cancer-derived multiple epitope-peptides cocktail vaccination clinical studies in patients with refractory/persistent disease of uterine cervical cancer and ovarian cancer [phase 2]

Oncoimmunology. 2020 Nov 11;9(1):1838189. doi: 10.1080/2162402X.2020.1838189.

Abstract

We had conducted phase 1/2 studies of cancer vaccination therapy using neo-tumor antigens in patients with refractory/persistent cervical cancer (CC) and ovarian cancer (OC) to assess the feasibility and efficacy. Enrollees must be refractory/persistent disease for usual treatments with Human Leukocyte Antigen-A*0201 or A*2402. The targets were epitope peptides obtained from driver genes in surviving pathways as follows: for CC A*0201, peptides from Up Regulating Lung Cancer 10 gene (URLC10) and Hypoxia-inducible gene 2 (HIG-2) and for OC A*0201, HIG2, VEGFR (vascular epithelial growth factor receptor) 1 and 2 were used. For CC A*2402, Forkhead Box M1 (FOXM1), Maternal Embryonic Leucine zipper Kinase (MELK), and Holliday Junction Recognition Protein (HJURP) were used. For OC A*2402, cocktails of peptides from FOXM1, MELK, HJURP, VEGFR1, and VEGFR2 were used. Subcutaneous administration was performed with adjuvant weekly. The toxicity profiles and tumor-response were analyzed in eight-week interval. Sixty-six patients were accrued, and 64 were evaluable for adverse events (AEs), and 35 for response. AEs of G2/3 dermatologic reaction (DR) of injection site had been identified in 15.6% and no other severe AEs were detected. Response rate in OC and CC were 22.9% and 20%, respectively. Median overall survival showed longer in performance status (PS) 0 (versus PS1/2), in CRP negative (versus positive) and in DR positive (versus negative) such as 8.7 m versus 1.2 m (p < .001), 8.8 m versus 3.0 m (p < .05) and 10.2 m versus 1.2 m (p < .001), respectively. In conclusion, our vaccination therapy was feasible and effective in this cohort of patients.

Keywords: HLA-A restricted peptides; cervical cancer; ovarian cancer; peptides vaccination immunotherapy; persistent; refractory.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epitopes
  • Female
  • Humans
  • Immunotherapy / adverse effects
  • Ovarian Neoplasms* / therapy
  • Peptides
  • Protein Serine-Threonine Kinases
  • Uterine Cervical Neoplasms* / therapy
  • Vaccination

Substances

  • Epitopes
  • Peptides
  • MELK protein, human
  • Protein Serine-Threonine Kinases

Grants and funding

The fund from Iwate Medical University School of Medicine Department of Obstetrics and Gynecology had supported this study