In situ vaccination at a peripheral tumor site augments response against melanoma brain metastases.

Journal for Immunotherapy of Cancer
Paul A ClarkZachary S Morris

Abstract

Immune checkpoint inhibition (ICI) alone is not efficacious for a large number of patients with melanoma brain metastases. We previously established an in situ vaccination (ISV) regimen combining radiation and immunocytokine to enhance response to ICIs. Here, we tested whether ISV inhibits the development of brain metastases in a murine melanoma model. B78 (GD2+) melanoma 'primary' tumors were engrafted on the right flank of C57BL/6 mice. After 3-4 weeks, primary tumors were treated with ISV (radiation (12 Gy, day 1), α-GD2 immunocytokine (hu14.18-IL2, days 6-10)) and ICI (α-CTLA-4, days 3, 6, 9). Complete response (CR) was defined as no residual tumor observed at treatment day 90. Mice with CR were tested for immune memory by re-engraftment with B78 in the left flank and then the brain. To test ISV efficacy against metastases, tumors were also engrafted in the left flank and brain of previously untreated mice. Tumors were analyzed by quantitative reverse transcription-PCR, immunohistochemistry, flow cytometry and multiplex cytokine assay. ISV+α-CTLA-4 resulted in immune memory and rejection of B78 engraftment in the brain in 11 of 12 mice. When B78 was engrafted in brain prior to treatment, ISV+α-CTLA-4 increased survival comp...Continue Reading

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Citations

Apr 4, 2021·Antibodies·Erin RunbeckSophie Papa
Jun 4, 2021·Neuromolecular Medicine·Alejandro J OnateZachary S Morris

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Methods Mentioned

BETA
surgical resection
X-Ray
ELISA
flow cytometry
PCR
dissection
transgenic

Clinical Trials Mentioned

NCT03958383

Software Mentioned

ImageJ
R
SPSS
SAS
MANTIS
FlowJo
Excel
Graphpad Prism

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