The idiotype of the immunoglobulin on a given B cell malignancy (Id) can serve as a clonal marker, and a previous pilot study in lymphoma pts. has demonstrated that autologous Id protein can be formulated into an immunogenic, tumor specific antigen by conjugation to a carrier protein (KLH) and administration with an emulsion-based adjuvant. The selection of GM-CSF as the immunological ?adjuvant? is a direct extension of our laboratory studies in small animal models demonstrating that GM- CSF can enhance the potency of the prototype Id- KLH vaccine by augmenting almost exclusively the cellular arm of the immune response. The objectives of this study are: 1) to evaluate cellular and humoral immune responses against the unique idiotype of the patients lymphoma and 2) to evaluate the ability of the Id vaccine to clear the bone marrow of malignant cells detectable by pathologic examination or molecular examination (polymerase chain reaction amplification of the rearranged bcl-2 oncogene). Previously untreated pts. with follicular lymphomas are treated to complete remission or minimal residual disease with ProMACE chemotherapy. 3 to 6 months after completion of chemotherapy, pts. receive an autologous Id vaccine conjugated with KLH with GM-CSF, administered s.c. locally with the vaccine on the day of vaccination and for the 3 consecutive days following vaccination, (pts. are randomized to either a high or low dose, 500 or 100 |g/m2). 20 pts. who achieved CR have completed the vaccination phase. In 17 patients, vaccination has elicited the first evidence for CD8+ T cells capable of lysing autologous lymphoma targets. Eight of 11 patients, whose tumors were mbr+, converted to PCR negativity, providing the first systematic evidence for an anti-tumor effect of Id vaccination.Publication: M.Bendandi et al., ?Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma,? Nature Medicine, 5:1171-7, October 1999 - Human Subjects
