CCTA-1 AND CCTA-2 ARE CANINE CANCER/TESTIS ANTIGENS
Paige Nemec, North Carolina State University
Paige Nemec1, Jennifer Holmes1, Alex Kapatos1, Paul Hess1
1. Department of Clinical Sciences, North Carolina State University, Raleigh NC
In solid tumors such as melanoma, only adoptive cell transfer (ACT) of ex vivoexpanded, autologous T cells has provided durable, complete responses in chemoresistant, advanced-stage patients. Targeting shared tumor-associated antigens (TAAs) offers the possibility of “off-the-shelf” ACT, but administration of T cells recognizing public differentiation TAAs have caused serious or fatal autoimmunity. Cancer-testis antigens (CTAs) are expressed during fetal development and in various cancers, but in few adult tissues, except for testis, an immunologically-privileged site. Tolerance and autoimmune risks are low, while sharing can be high, an ideal TAA profile. Using mass spectrometry to probe a canine histiocytic cell line, we found peptide signatures of 4 established human CTAs, and 12 other proteins whose human orthologs appear to be tissuerestricted (testis; testis/brain), according to multiple expression databases. We hypothesized that some may be novel, genuine canine CTAs in histiocytic sarcoma (HS), and evaluated mRNA expression of the 5 most-promising candidates (CCTAs 1-5) by qPCR in HS biopsies and a variety of normal tissues. In 10 HS samples, 9, 10 and 7 expressed CCTA-1, CCTA-2 and CCTA-3, respectively. CCTA-1 was highly expressed in two privileged sites (testis and brain), minimally expressed in the pituitary and marrow, and not detected in most somatic tissues or in the tumor parent, DCs. CCTA-2 was similar, but with higher expression in bone marrow. Other candidates had unfavorable peripheral expression (CCTA-3, CCTA-4) or were not found in HS samples (CCTA-5). CCTA-1 and CCTA-2 represent classical CTAs in the dog and can be developed as ACT targets.