BibTex format
@article{Ishihara:2018:10.1158/1535-7163.mct-18-0091,
author = {Ishihara, J and Ishihara, A and Potin, L and Hosseinchi, P and Fukunaga, K and Damo, M and Gajewski, TF and Swartz, MA and Hubbell, JA},
doi = {10.1158/1535-7163.mct-18-0091},
journal = {Molecular Cancer Therapeutics},
pages = {2399--2411},
title = {Improving efficacy and safety of agonistic anti-CD40 antibody through extracellular matrix affinity},
url = {http://dx.doi.org/10.1158/1535-7163.mct-18-0091},
volume = {17},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - CD40 is an immune costimulatory receptor expressed by antigen-presenting cells. Agonistic anti-CD40 antibodies have demonstrated considerable antitumor effects yet can also elicit serious treatment-related adverse events, such as liver toxicity, including in man. We engineered a variant that binds extracellular matrix through a super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144) to enhance anti-CD40′s effects when administered locally. Peritumoral injection of PlGF-2123-144-anti-CD40 antibody showed prolonged tissue retention at the injection site and substantially decreased systemic exposure, resulting in decreased liver toxicity. In four mouse tumor models, PlGF-2123-144-anti-CD40 antibody demonstrated enhanced antitumor efficacy compared with its unmodified form and correlated with activated dendritic cells, B cells, and T cells in the tumor and in the tumor-draining lymph node. Moreover, in a genetically engineered BrafV600E βCatSTA melanoma model that does not respond to checkpoint inhibitors, PlGF-2123-144-anti-CD40 antibody treatment enhanced T-cell infiltration into the tumors and slowed tumor growth. Together, these results demonstrate the marked therapeutic advantages of engineering matrix-binding domains onto agonistic anti-CD40 antibody as a therapeutic given by tumori-regional injection for cancer immunotherapy.
AU - Ishihara,J
AU - Ishihara,A
AU - Potin,L
AU - Hosseinchi,P
AU - Fukunaga,K
AU - Damo,M
AU - Gajewski,TF
AU - Swartz,MA
AU - Hubbell,JA
DO - 10.1158/1535-7163.mct-18-0091
EP - 2411
PY - 2018///
SN - 1535-7163
SP - 2399
TI - Improving efficacy and safety of agonistic anti-CD40 antibody through extracellular matrix affinity
T2 - Molecular Cancer Therapeutics
UR - http://dx.doi.org/10.1158/1535-7163.mct-18-0091
UR - https://mct.aacrjournals.org/content/17/11/2399
VL - 17
ER -