Expression of Cancer Testis (CT) Antigens NY-ESO-1 and LAGE-1 in Multiple Myeloma (MM): Could a Vaccine against the Former Antigen Be Effective against the Latter?

In recent years, the expression of CT antigens has been studied in various malignant neoplasias. Based on their tumor-associated expression and due to their ability to elicit an immune response in the autologous host, CT antigens are potential targets for vaccine-based immunotherapy of cancer. Since different CT antigens can be expressed simultaneously in the same tumor, CT antigens are possible targets for polyvalent vaccines. Immunotherapy trials employing MAGE-A3 and NY-ESO-1 in MM patients are in progress. We previously reported frequent expression of LAGE-1 on mRNA level in MM patients (∼50%). Due to the high similarity between NY-ESO-1 and LAGE-1 (94% in mRNA and 84% in protein sequences) and the more prevalent presence of the latter, it is interesting to speculate if anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be efficient in patients with LAGE-1-positive tumors.

To evaluate mRNA and protein expression of NY-ESO-1 and LAGE-1 in MM patients and to explore the possibility of an anti-NY-ESO-1 vaccine eliciting immunity to LAGE-1.

The expression of NY-ESO-1 and LAGE-1 was studied by RT-PCR in 18 normal tissues, 28 bone marrow MM samples and U266 cell line. NY-ESO-1 and LAGE-1 protein expression were analyzed by immunohistochemistry in the MM specimens using monoclonal antibody (mAb) E978 and mAb 219-510-23 respectively. The protein extracts from U266 (NY-ESO-1+/LAGE-1+), H1299 (only NY-ESO-1+), SKBR3 (only LAGE-1+) and HaCat (double negative) cell lines were analyzed by Western Blot with mAb E978 (1:5,000).

RT-PCR was positive for both genes in testis, placenta and U266 cell line. All other normal tissues were negative. In MM, LAGE-1 was positive in 36% (10/28) and NY-ESO-1 in 18% (5/28) of total bone marrow samples. However, only 2 patients (7%) were positive for protein expression by immunohistochemistry (both cases were also positive by RT-PCR). Both NY-ESO-1 mRNA-positive cell lines U266 and H1299 were positive by Western Blot for mAb E978, but this anti-NY-ESO-1 mAb was unable to identify LAGE-1 protein in U266 and SKBR3 cell line extracts.

In this small group of MM patients, NY-ESO-1 and LAGE-1 were expressed on mRNA level in 18% and 36% respectively, while both antigens were present on protein level in only 7%. Discrepancies between RNA and protein expression has been described in other tumors for CT antigens previously. The incidence of up to 36% LAGE-1 positive cases suggest that multiple myeloma might be susceptible to LAGE-1 and/or NY-ESO-1 vaccine-based immunotherapy. Also it is may be possible that, due to the high similarity between the proteins, anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be efficient in patients with LAGE-1-positive tumors.

No relevant conflicts of interest to declare.