Abstract 1316: Evaluation of immune cell subsets of cancer patients treated with a fully human IgG1 anti-PD-L1 MAb (MSB0010718C) capable of mediating ADCC of human tumor cells
Authors: Lepone Lauren M. , Donahue Renee N. , Farsaci Benedetto , Grenga Italia , Boyerinas Benjamin , Jochems Caroline , Tsang Kwong-Yok , Heery Christopher R. , Madan Ravi A. , O'Sullivan Coyne Geraldine , Singh Harpreet , Gulley James L. , Schlom Jeffrey 
Published: August 2015

Background: Several monoclonal antibodies (MAbs) with demonstrated clinical anti-cancer activities have been engineered as fully human IgG1 entities to also encompass their potential to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells. MSB0010718C is a fully human IgG1 MAb targeting the co-regulatory protein Programmed Death-Ligand 1 (PD-L1), and is thus distinct from other MAbs targeting the PD-L1/PD-1 axis currently being evaluated in clinical trials. One possibility is that an anti-PD-L1 antibody capable of inducing ADCC may negatively affect PD-L1 expressing immune cell subtypes. This work is intended to determine if there is any validity to this concern. Methods: The clinical activity of MSB0010718C, observed in several tumor types in ongoing clinical studies such as NCT01772004, has been and will be reported elsewhere. In the studies reported here, MSB0010718C is shown to mediate ADCC of several types of human tumor cell lines (e.g., breast, lung, bladder carcinomas) in vitro, with tumor cell lysis mediated mainly by human CD16+ monocytes and natural killer (NK) cells. Since some human immune cell subsets express PD-L1 on their cell surface (albeit at relatively low levels compared to many tumor cells), studies were undertaken to evaluate changes in the frequency of immune cell subsets in peripheral blood mononuclear cells (PBMC) from cancer patients pre- vs post-treatment with MSB0010718C. Immune cells evaluated were PD-L1 positive and PD-L1 negative subsets of the following: CD4+ T cells, CD8+ T cells, NK cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), natural killer T cells (NKT), plasmacytoid dendritic cells (DC), conventional DC, and B cells. Results: Forty-two post-treatment PBMC samples were evaluated as follows: pre vs 1 dose of MSB0010718C (day 15, n = 19); pre vs 3 doses of MSB0010718C (day 43, n = 14); and pre vs 9 doses of MSB0010718C (day 127, n = 9). In all cases there were no statistical differences pre- vs post-treatment in any immune cell subset, and at any time point analyzed, regardless of whether the immune subset expressed PD-L1 or not. In addition, no changes were observed in absolute lymphocyte counts at any time point analyzed. Conclusion: While immune cell subsets pre- vs post-treatment continue to be analyzed in various patient cohorts, these studies provide evidence that MSB0010718C, a fully human IgG1 MAb, capable of mediating ADCC, can be administered safely to cancer patients without altering the balance of numerous PBMC immune cell subsets.

Citation Format: Lauren M. Lepone, Renee N. Donahue, Benedetto Farsaci, Italia Grenga, Benjamin Boyerinas, Caroline Jochems, Kwong-Yok Tsang, Christopher R. Heery, Ravi A. Madan, Geraldine O'Sullivan Coyne, Harpreet Singh, James L. Gulley, Jeffrey Schlom. Evaluation of immune cell subsets of cancer patients treated with a fully human IgG1 anti-PD-L1 MAb (MSB0010718C) capable of mediating ADCC of human tumor cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1316. doi:10.1158/1538-7445.AM2015-1316