Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma.

Autor:	Albertini MR; University of Wisconsin Carbone Cancer Center.; Departments of, Medicine.; Dermatology, University of Wisconsin School of Medicine and Public Health.; The Medical Service, William S. Middleton Memorial Veterans Hospital., Zuleger CL; University of Wisconsin Carbone Cancer Center.; Departments of, Medicine., Ranheim EA; University of Wisconsin Carbone Cancer Center.; Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin., Shiyanbola O; Department of Pathology, Stanford University School of Medicine, Stanford, California., Sondel PM; University of Wisconsin Carbone Cancer Center.; Departments of Pediatrics.; Human Oncology., Morris ZS; University of Wisconsin Carbone Cancer Center.; Human Oncology., Eickhoff J; University of Wisconsin Carbone Cancer Center.; Biostatistics & Medical Informatics., Newton MA; University of Wisconsin Carbone Cancer Center.; Biostatistics & Medical Informatics., Ong IM; University of Wisconsin Carbone Cancer Center.; Biostatistics & Medical Informatics.; Obstetrics & Gynecology, University of Wisconsin School of Medicine and Public Health., Schwartz RW; Biostatistics & Medical Informatics., Hayim R; Departments of Medical Sciences., Kurzman ID; Departments of Medical Sciences., Turek M; Surgical Sciences, University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin, USA., Vail DM; University of Wisconsin Carbone Cancer Center.; Departments of Medical Sciences.
Jazyk:	angličtina
Zdroj:	Melanoma research [Melanoma Res] 2024 Aug 01; Vol. 34 (4), pp. 307-318. Date of Electronic Publication: 2024 May 20.
DOI:	10.1097/CMR.0000000000000975
Abstrakt:	Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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