Article

The clinical relevance of humoral immune responses to Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 and expression of Globo H in metastatic breast cancer

Jung‐Tung HungInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanI‐Ju ChenShir‐Hwa UengDepartment of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanChiun‐Sheng HuangDepartment of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanShin‐Cheh ChenDepartment of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanMu‐Yi ChenYung‐Chang LinDepartment of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanChun‐Yen LinDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, TaiwanMichael J. CampbellDepartment of Surgery, Division of Surgical Oncology, University of California San Francisco, San Francisco, California, USAHope S. RugoHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USAAlice L. YuDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA

2022en

ABI

Abstract

An international randomized phase II trial of Globo H (GH) vaccine, adagloxad simolenin/OBI-821 in 349 patients with metastatic breast cancer showed longer progression-free survival (PFS) in vaccinated patients who developed anti-Globo H (anti-GH) IgG than those who did not and the placebo group. The impacts of anti-GH IgM and GH expression on peak anti-GH IgG and clinical outcome were further evaluated. The titers of anti-GH IgG and IgM were determined by ELISA. GH expression in tumor was examined by immunohistochemical staining. Immunophenotyping was conducted by flow cytometry. Adagloxad simolenin elicited anti-GH IgM which peaked at titers ≥1:80 between weeks 5 and 13. The mean anti-GH IgG titer peaked at week 41 and decreased thereafter on the completion of vaccination. One log increase in peak IgM was associated with 10.6% decrease in the HR of disease progression (HR: 0.894, 95% CI: 0.833 to 0.960, p=0.0019). Patients with anti-GH IgM ≥1:320 within first 4 weeks after vaccination had significantly higher maximum anti-GH IgM (p<0.0001) and IgG titers (p<0.0001) than those with <1:320. Moreover, the median PFS appears to be longer for patients with anti-GH IgM ≥1:320 within first 4 weeks than those with anti-GH IgM titer <1:320 (11.1 vs 7.3 months, p=0.164), but not statistically significant. Among patients with H score ≥80 for GH expression by immunohistochemistry, the vaccination group (n=42) seemed to have better PFS than the placebo group (n=23) (HR=0.59; 95% CI: 0.32 to 1.10, p=0.10), but the difference did not reach statistical significance. In addition, peak levels of anti-GH IgM were higher in patients who had lower percentage of activated regulatory T cells (Treg cells; CD4 + CD45RA - Foxp3 high ) at baseline than those who had higher activated Treg cells (p=0.042). This study demonstrates that adagloxad simolenin induced both IgG and IgM antibodies against GH. Anti-GH IgM ≥1:320 within first 4 weeks or low activated Treg cells at baseline may help to select patients who are likely to produce a higher level of GH-specific IgM and IgG in the future.

Identifiers

DOI: 10.1136/jitc-2021-004312

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