Vaccine strategies in the treatment of low-grade non-Hodgkin lymphoma.

Recent years have witnessed the development of a variety of promising immunotherapies for treating patients with B-cell non-Hodgkin's lymphomas. Each B lymphocyte expresses an immunoglobulin molecule that is the product of a unique combination of gene segments. B cell malignancy arises from one original B lymphocyte, and therefore all the members of a given lymphoma tumor population have the same unique immunoglobulin, which can serve as a target for immune therapy. When the idiotype (Id), or unique portion, of each immunoglobulin is used as a vaccine, antibodies and T cells can be induced and each can cause rejection of the tumor by the host. This special opportunity for tumor specificity is accompanied by the challenge of constructing a different vaccine for each patient. The first clinical trial of Id vaccination for lymphoma was initiated at Stanford University in 1988. Tumor cells obtained from lymph node sampling were fused with a myeloma cell line to generate a "hybridoma" producing large quantities of idiotype protein. Purified Id protein was then chemically coupled to keyhole limpet hemocyanin (KLH) and emulsified in an "oil-in-water" type immunologic adjuvant. The initial trial included patients with low-grade, follicular lymphoma, in first remission following chemotherapy. Among the first 32 vaccinated patients, roughly half (14/32) developed anti-Id immune responses. These were principally humoral responses rather than cellular responses. Long-term follow-up of these 32 patients has revealed that the development of an immune response is strongly correlated with prolonged freedom from disease progression interval and overall survival. Further trials have confirmed significant clinical benefit following Id vaccination. There is reason for excitement about the prospects for effective vaccine therapies for lymphoma as randomized Id vaccine trials commence and newer cell-based vaccine trials enter the clinic. As the clinical activity of lymphoma vaccines becomes established, it will be important to determine how to best integrate active vaccination approaches with standard therapeutic approaches.