title: The novel cancer-testis antigen A-kinase anchor protein 4 (AKAP4) is a potential target for immunotherapy of ovarian serous carcinoma.
abstract: Ovarian cancer is one of the neoplasms affecting the reproductive tract associated with high mortality rate because of limited therapeutic options and an elevated incidence of chemoresistance and recurrence. In this context, immunotherapy may constitute a promising approach to improve survival rates and clinical outcome, raising the need for specific target antigens. Cancer-testis antigens (CTAs) are considered promising candidates in this sense because they are aberrant expressed by various malignancies but not by non-transformed tissue, with the exception of testes. Here, we examined the expression and potential to promote humoral immune responses of a novel CTA, A-kinase anchor protein 4 (AKAP4), among 38 ovarian carcinoma patients. Our results reveal that AKAP4 was expressed at both the mRNA and protein levels in 89% (34/38) of ovarian carcinoma tissue specimens but not in 21 matched adjacent non-cancerous tissues. In addition, a humoral response against AKAP4 was detected in 58% (22/38) of ovarian carcinoma patients by ELISA. In particular, 65% (22/34) patients bearing an AKAP4-expressing tumor exhibited circulating anti-AKAP4 antibodies. Interestingly, the majority of specimens were categorized as ovarian serous adenocarcinoma and serous papillary carcinoma, of which 93% (28/30) and 100% (6/6), respectively, expressed AKAP4. A humoral response against AKAP4 was detected in 79% (19/24) and 67% (4/6) of ovarian serous adenocarcinoma and serous papillary carcinoma patients, respectively. The presence of circulating anti-AKAP4 antibodies suggests the AKAP4 is highly immunogenic in ovarian serous carcinoma patients. Our study lays the foundations for exploring AKAP4 as a potential target for the immunotherapy of ovarian cancer.
authors.affiliation: Cancer Microarray; Genes and Proteins Laboratory; National Institute of Immunology; Aruna Asaf Ali Marg; New Delhi, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Agarwal
authors.forename: Shikha
authors.initials: S
authors.lastname: Saini
authors.forename: Deepak
authors.initials: D
authors.lastname: Parashar
authors.forename: Archana
authors.initials: A
authors.lastname: Verma
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Sinha
authors.forename: Nirmala
authors.initials: N
authors.lastname: Jagadish
authors.forename: Aruna
authors.initials: A
authors.lastname: Batra
authors.forename: Sushma
authors.initials: S
authors.lastname: Suri
authors.forename: Anju
authors.initials: A
authors.lastname: Gupta
authors.forename: Abdul S
authors.initials: AS
authors.lastname: Ansari
authors.forename: Nirmal Kumar
authors.initials: NK
authors.lastname: Lohiya
authors.forename: Anil
authors.initials: A
authors.lastname: Suri
keywords: AKAP4; cancer-testis antigen; immunotherapy; ovarian serous carcinoma; vaccine