Immune Therapy

Direct targeting of tumor cells with naked antibody (Ab) or immunoconjugate remains an attractive approach to the treatment of malignant disease. In the treatment of NHL, this approach has proven benefit in the use of the monoclonal antibody (MAb) rituximab and the immunoconjugate ZevalinĀ® (90Yttrium ibritumomab tiuxetan), both of which target the CD20 molecule present on B lymphocytes. Methods to augment the patient's own immune responses are also under investigation (9,46-49).

Preclinical data suggest that one approach to stimulating the host immune response to the malignant clone is through the use of HGFs (46,50). rHuGM-CSF has been shown to enhance the neutrophil functions of phagocytosis and chemotaxis, to increase the cytotoxicity and cytokine production of monocytes, and to boost the quantity and function of antigen-presenting cells (46). This finding is important given that monocytes have been shown to have defective phagocytic activity in patients with NHL (50). Additionally, both rHuG-CSF and rHuGM-CSF have been shown to augment antibody-dependent cellular cytotoxicity (ADCC), a mechanism of action of rituximab and other MAbs (49,51,52).

Another approach to generating a host immune response to the malignant lymphoma is through the administration of tumor-specific vaccines. The malignant cells in NHL display antigenic determinants, or idiotypes, which are tumor specific and serve as targets for the immune system (47,48). Several studies have shown clinical benefit with production of antitumor immunologic responses consisting of both humoral and cyto-toxic T-cell responses (9,47,48,53,54). Bendandi and colleagues (9) demonstrated that the immunization of patients using a follicular lymphoma idiotype-specific vaccine supplemented with rHuGM-CSF resulted in molecular complete response in 8/11 patients who before immunization were positive for t(14;18). Furthermore, 19/20 immunized patients developed tumor-specific cytotoxic T-cell responses. They hypothesized that the addition of rHuGM-CSF to the vaccine results in recruitment of antigen-presenting cells and subsequent stimulation of a T-cell response. It has been previously suggested that the T-cell response is the basis for disease control with idiotype vaccines both in murine studies and early clinical trials and that this response is augmented by the addition of rHuGM-CSF (54,55). The use of immune modulation in the treatment of lymphoma is under continued investigation. The supplementation of these mechanisms with HGF needs to be studied further.

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