التفاصيل البيبلوغرافية
| العنوان: |
A phase 1 study of NY-ESO-1 vaccine + anti-CTLA4 antibody Ipilimumab (IPI) in patients with unresectable or metastatic melanoma. |
| المؤلفون: |
Slingluff jr, Craig L.1 cls8h@virginia.edu, Zarour, Hassane M.2, Tawbi, Hussein Abdul-Hassan2,3, Kirkwood, John M.2, Postow, Michael A.4, Friedlander, Philip5, Devoe, Craig E.6, Gaughan, Elizabeth M.7, Mauldin, Ileana S.1, Olson jr, Walter C.1, Smith, Kelly T.1, Macri, Mary J.8, Ricciardi, Toni8, Ryan, Aileen8, Venhaus, Ralph8, Wolchok, Jedd D.4,9,10 |
| المصدر: |
OncoImmunology. 2021, Vol. 10 Issue 1, p1-12. 12p. |
| مصطلحات موضوعية: |
*MELANOMA, *T cells, *IPILIMUMAB, *CANCER vaccines, *EXPERIMENTAL design, *TUMOR microenvironment |
| مستخلص: |
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 RORyt+ 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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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