Abstract 2592: Tumor targeting and pharmacodynamics of the novel targeted immunocytokine FAP-IL2v in a tumor-bearing Rhesus monkey (2014)

Abstract FAP-IL2v is a novel monomeric FAP-targeted immunocytokine where a single, engineered IL-2 variant (IL-2v) with abolished IL-2Ralpha (CD25) binding is fused to the C-terminus of an high affinity anti-FAP antibody (1). FAP-IL2v was designed to selectively bind to the tumor thereby avoiding the systemic toxicity inherent to systemic administration of cytokines. The goal of this study was to assess the tumor targeting and pharmacodynamic properties of FAP-IL2v in an appropriate tumor bearing animal model. Explanted tumor xenografts in mice do not have high expression of FAP and lack the complete immune system which is important to assess the safety, efficacy, and biodistribution of these targeted immunocytokines. Therefore, we elected to use monkeys with spontaneous tumors for this study. Herein, we report a first of kind study in monkeys with spontaneous tumors to better understand tumor targeting and pharmacodynamics of FAP-IL2v. Three monkeys with a history of cancer and suspected relapse were identified. Immunohistochemistry was done on archival tumor tissue to assess target (FAP) expression and FDG-PET performed to detect metastatic lesions. Based on the positive FAP expression on tumor tissue and detectable tumor lesions and lesion locations from FDG-PET scans, a rhesus monkey with metastatic breast cancer was selected for further experimentation with FAP-IL2v. The monkey was administered with 0.5 mg/kg of FAP-IL2v mixed with tracer amounts of 89Zr labeled FAP-IL2v for assessment of tumor targeting using PET imaging. Baseline and on-treatment blood samples and tumor biopsies were collected after single-administration for assessment of pharmacodynamic effects. The study revealed that FAP-IL2v selectively targets and accumulates in the tumor lesions with minimal uptake in the lungs, spleen and lymphoid tissues (major sink organs and potential risk factors). All three FDG-avid lesions showed accumulation of FAP-IL2v over 6 days with peak uptake of SUV= 3.1 at day 3. After single administration, transient lymphocytosis and peripheral expansion of immune cells were observed. Analyses of tumor biopsies suggested increased immune cell infiltration. No signs of distress or cytokine release were observed during the treatment period. In conclusion, using a monkey with spontaneous tumors, we demonstrated that the FAP-IL2v targeted immunocytokine can selectively be delivered to tumor and induce intended changes in immune microenvironment without major adverse events. (1) C. Klein et al., Tumor-targeted, engineered IL-2 variant (IL-2v)-based immunocytokines for the immunotherapy of cancer, AACR 2013, Poster 486 Citation Format: Stefan Evers, Pradeep K. Garg, J. Mark Cline, Sudha Garg, Greg Dugan, Anne Freimoser-Grundschober, Natalie D. Keirstead, Christian Klein, Tapan Nayak. Tumor targeting and pharmacodynamics of the novel targeted immunocytokine FAP-IL2v in a tumor-bearing Rhesus monkey. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2592. doi:10.1158/1538-7445.AM2014-2592