Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma

Purpose: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA -iLR) is a multifunctional protein expressed by various tumors, including b reast, lung ovary and prostate carcinoma as well as lymphoma. OFA-iLR has b een implicated in tumor invasiveness, metastasis and growth. Interferon-gam ma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. Materials and Methods: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune re sponses against OFA-iLR were determined in patients with metastatic renal c ell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) resp onses of peripheral blood mononuclear cells from patients with renal cell c arcinoma against recombinant OFA-iLR were assessed. Results: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell ca rcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytoki ne responses of mononuclear cells were detected in all 6 patients tested. I mportantly evidence was also obtained that treating metastatic renal cell c arcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR spe cific immunity. Conclusions: This study demonstrates that OFA-iLR is an immunogenic tumor a ssociated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolera nce and, thus, tumor progression.