期刊
ONCOIMMUNOLOGY
卷 10, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.1898105
关键词
Immunotherapy; active∙ Melanoma∙ Vaccination; Antibody specificity∙ Tumor Microenvironment
资金
- Ludwig Institute for Cancer Research
- National Institutes of Health [P30 CA44579, P30 CA008748]
- Cancer Research Institute
- University of Virginia Cancer Center Support Grant [NIH/NCI P30 CA44579]
- Memorial Sloan Kettering Cancer Center (New York, USA): Cancer Center Support Grant [NP30 CA008748]
- Ludwig Collaborative and Swim Across America Laboratory, Parker Institute for Cancer Immunotherapy
- Department of Medicine
Treatment with IPI + NY-ESO-1 vaccines enhanced T cell and antibody responses in patients. Patients with best clinical responses had broader antibody responses and increased T cell densities.
Ipilimumab (IPI) can enhance immunity to the cancer-testis antigen NY-ESO-1. A clinical trial was designed to assess safety, immunogenicity, and clinical responses with IPI + NY-ESO-1 vaccines and effects on the tumor microenvironment (TME). Patients with measurable NY-ESO-1(+) tumors were enrolled among three arms: A) IPI + NY-ESO-1 protein + poly-ICLC (pICLC) + incomplete Freund's adjuvant (IFA); B) IPI + NY-ESO-1 overlapping long peptides (OLP) + pICLC + IFA; and C) IPI + NY-ESO-1 OLP + pICLC. Clinical responses were assessed by irRC. T cell and Ab responses were assessed by ex vivo IFN-gamma ELIspot and ELISA. Tumor biopsies pre- and post-treatment were evaluated for immune infiltrates. Eight patients were enrolled: 5, 2, and 1 in Arms A-C, respectively. There were no DLTs. Best clinical responses were SD (4) and PD (4). T-cell and antibody (Ab) responses to NY-ESO-1 were detected in 6 (75%) and 7 (88%) patients, respectively, and were associated with SD. The breadth of Ab responses was greater for patients with SD than PD (p = .036). For five patients evaluable in the TME, treatment was associated with increases in proliferating (Ki67(+)) CD8(+) T cells and decreases in ROR gamma t(+) CD4(+) T cells. T cell densities increased for those with SD. Detection of T cell responses to NY-ESO-1 ex vivo in most patients suggests that IPI may have enhanced those responses. Proliferating intratumoral CD8(+) T cells increased after vaccination plus IPI suggesting favorable impact of IPI plus NY-ESO-1 vaccines on the TME.
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