Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery
2019
An anti-glucocorticoid induced TNF receptor (GITR) agonistic antibody (
Ab) induces an antitumor immunity with both stimulation of effector T cells and inhibition of regulatory T cell activity. To enhance GITR
Ab-mediated tumor immunity, we focused on the intratumoral route, since a tumor-localized high concentration of
Abwould confer activation of only tumor-infiltrating T cells. First, in a murine colon cancer model, we showed that the intratumoral delivery of
Absignificantly increased the number of effector T cells infiltrated into tumors, and suppressed tumor growth more effectively than the intraperitoneal and intravenous injections did. Then, we found that the injection of
Abinto the peritumoral area induced a systemic antitumor immunity at a similar level to the intratumoral injection. Therefore, we hypothesized that the transfer of locally administrated
Abinto tumor-draining lymph nodes (TDLNs) plays an important role in inducing an effective immunity. In fact, intratumorally or peritumorally injected
Abwas detected in TDLNs, and resection of
Ab-injected TDLNs significantly reduced GITR
Ab-mediated systemic tumor immunity. Intratumoral injection showed less number of auto-reactive T cells in the spleen than the intraperitoneal injection did. Intratumoral delivery of GITR
Abis a promising approach to induce an effective immunity compared to the systemic delivery.
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