Abstract 1686: CD70 as a target in non-Hodgkin lymphoma (NHL) and renal cell carcinoma (RCC)

Abstract

Abstract Background CD70 is a member of the TNF superfamily expressed primarily on activated lymphocytes. CD70 interacts with CD27 to regulate B and T cell functions. Among normal, nonlymphoid tissues, CD70 is only expressed on stromal cells of the thymic medulla and mature dendritic cells. CD70 expression in RCC and NHL highlights its potential as a target for cancer therapy. Methods An indirect immunohistochemistry (IHC) assay was developed using an anti-CD70 mouse monoclonal antibody (Ryan 2010), and validated in a CLIA-compliant laboratory. Control cell lines had receptor numbers and IHC staining intensities of ∼190,000 (3+), ∼21000 (3+), ∼4000 (1+) and 0 (0). Archived tumor tissue from consenting patients with relapsed/refractory (RR) NHL or metastatic RCC were stained and read by a board-certified pathologist at Quest Diagnostics, reporting the percentage of cells staining for CD70, intensity, and subcellular localization of the stain. Results The rates and homogeneity of combined membrane and non-membrane CD70 staining intensity ≥1+ and 3+ for each tumor type are shown in the table below. The majority of NHL (88%) and RCC (80%) samples exhibited membranous CD70 staining ≥1+; >75% exhibited 3+ staining. Among the NHL and RCC subtypes sampled, high levels of 3+ intensity were observed in diffuse large B cell lymphoma (DLBCL; N = 44, 84%), follicular lymphoma (FL; N = 26, 77%), mantle cell lymphoma (MCL; N = 6, 67%), clear cell RCC (ccRCC; N = 138, 93%), and papillary RCC (pRCC; N = 15, 67%). No chromophobe RCC samples showed membranous staining (N = 5). CD70 expression in NHL and RCC tumor samples% cells in sample expressing CD70Samples positive for membrane and non-membrane CD70 expression, n (%)NHLRCCDLBCL, N = 44Other NHL, N = 41Clear Cell, N = 138Other RCC, N = 32>/ = 1+ intensity3+ intensity>/ = 1+ intensity3+ intensity>/ = 1+ intensity3+ intensity>/ = 1+ intensity3+ intensity02 (5)7 (16)6 (15)12 (29)4 (3)9 (7)11 (34)14 (44)1-209 (20)10 (23)11 (27)17 (41)12 (9)26 (19)7 (22)7 (22)21-404 (9)6 (14)8 (20)3 (7)14 (10)19 (14)2 (6)3 (9)41-604 (9)3 (7)3 (7)4 (10)10 (7)18 (13)2 (6)5 (16)61-807 (16)7 (16)5 (12)1 (2)12 (9)26 (19)4 (13)2 (6)81-10018 (41)11 (25)8 (20)4 (10)86 (62)40 (29)6 (19)1 (3) Conclusions CD70 is expressed in the majority of DLBCL, FL, MCL, ccRCC, and pRCC samples tested. Based on the unmet medical needs of these diseases, limited expression of CD70 on normal tissues, predominant membrane expression of CD70, and observed preclinical antitumor activity (Jeffrey 2013), a CD70-targeted antibody-drug conjugate, SGN-CD70A, has been advanced into clinical development in CD70-positive RR NHL and metastatic RCC (NCT# NCT02216890). Citation Format: Kenneth W. Wood, Elaina M. Gartner, Mechthild Jonas, Maureen Ryan, Dana A. Kennedy. CD70 as a target in non-Hodgkin lymphoma (NHL) and renal cell carcinoma (RCC). [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 1686. doi:10.1158/1538-7445.AM2015-1686