Malignant tumors often express characteristic antigens or "markers" which offer a mechanism for tumor prevention, resistance or treatment. The antigens which are characteristic of the tumor may be purified and formulated into vaccines. This may stimulate an antibody response and a cellular immune response which are helpful in controlling tumor growth. At a minimum, the antibodies raised by these antigens can be used as detection tools to monitor the level of tumor marker in the host to track the course of the disease or the effectiveness of treatment.
It is well known that the immunogenicity of antigens can be enhanced by coupling these hapten-bearing moieties to carriers. A variety of carriers are routinely used, such as keyhole limpet hemocyanin and various serum albumins. It is also understood that certain cytokines, such as GM-CSF, have the capacity to enhance primary antibody responses to antigens (Morrissey, P. J., et al, J Immunol (1987) 139: 1113-1119).
The immune response-enhancing ability of a cytokine, when coupled to a viral antigen, has been shown by Hinuma, S., et al, FEBS (1991) 288: 138-142. In this work, interleukin-2 was coupled to a herpes simplex virus type I glycoprotein by generating a fusion protein consisting of the glycoprotein D and human IL-2. The conjugate was shown to induce high antibody responses and cell-mediated immunity to HSV-I in mice.
It has now been found that B cell lymphoma tumor-associated antigens can be coupled to immune response-enhancing cytokines, such as GM-CSF, IL-2 and IL-4, to produce an immune response to the tumor antigen and enhance the ability of the host to resist tumor growth associated with the antigen.