Article


Evaluation of LAGE-1 and NY-ESO-1 expression in multiple myeloma patients to explore possible benefits of their homology for immunotherapy

Fabricio de Carvalho1, Andre L. Vettore2, Riguel J. Inaoka1, Bruno Karia2, Valéria C. C. Andrade1, Sacha Gnjatic3, Achim A. Jungbluth3 and Gisele W. B. Colleoni1

1Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

2Departamento de Biologia, Campus Diadema, UNIFESP, Diadema, Brazil

3Ludwig Institute for Cancer Research, New York, NY, USA

Communicated by: A Knuth

Keywords: human, multiple myeloma, CT antigens, RT-PCR, immunohistochemistry, ELISA


Abstract

Due to the high homology between the LAGE-1 and NY-ESO-1 proteins, we hypothesized that an anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be effective in multiple myeloma (MM) patients with LAGE-1-positive/NY-ESO-1-negative tumors. Therefore, we set out to evaluate LAGE-1 and NY-ESO-1 mRNA and protein expression in MM patients in a bid to evaluate possible benefits of their homology for immunotherapy. LAGE-1 (a and b isoforms) and NY-ESO-1 mRNA expression was studied in 18 normal tissues and 50 bone marrow MM samples by RT-PCR. LAGE-1 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in 27 MM specimens using mAbs 219-510-23 and E978. Spontaneous serological immune response against both antigens was analyzed by ELISA in sera from 33 MM patients. LAGE-1 (a and b isoforms) was positive in 42% and NY-ESO-1 in 26% of the MM samples analyzed by RT-PCR. Both genes were found to be expressed in 18% of the cases, while at least one of the genes was found to be expressed in 50% of the cases. In LAGE-1 positive samples, 81% were positive for LAGE-1a and 19% were positive for both LAGE-1a and -1b. LAGE-1 and NY-ESO-1 protein expression could only be detected in two cases by IHC and there was a clear strong spontaneous antibody response to LAGE-1 and NY-ESO-1 in only one MM patient. In conclusion, LAGE-1a and NY-ESO-1 homology cannot be easily exploited in an anti-NY-ESO-1 vaccine given the low frequency of protein expression detected by IHC or serum analysis.