Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer.

Abstract

Brain, lung, and colon tissue experience deleterious immune-related adverse events when immune-oncological agents or radiation are administered. However, there is a paucity of information regarding whether the addition of radiation to immuno-oncological regimens exacerbates the tissue inflammatory response. We used a murine model to evaluate sub-acute tissue damage and the systemic immune response in C57Bl/6 mice when administered systemic anti-programmed cell death protein 1 (αPD-1) immunotherapy alone or in combination with stereotactic fractionated 10 gray/5 X-ray radiation to normal brain, lung or colon tissue. The model indicated that combinatorial αPD-1 immunotherapy and radiation may alter normal colon cell proliferation and cerebral blood vasculature, and induce systemic thrombocytopenia, lymphopenia, immune suppression, and altered immune repertoire (including interleukin-1β). Therein our data supports close monitoring of hematological and immune-related adverse events in patients receiving combination therapy.

• Authors: Kelly J McKelvey, Amanda L Hudson, Ramyashree Prasanna Kumar, Thomas Eade, Stephen J Clarke, Helen R Wheeler, Connie I Diakos, Viive M Howell
• Journal: Frontiers in oncology (Front Oncol) Vol. 9 Pg. 1504 ( 2019) ISSN: 2234-943X [Print] Switzerland
• PMID: 32010614 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 McKelvey, Hudson, Prasanna Kumar, Eade, Clarke, Wheeler, Diakos and Howell.