Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: implications for lymphomagenesis.

We observed novel transformations of follicular lymphoma (FL), first, a switch in immunoglobulin (Ig) light chain, and second, transformation of FL to acute lymphoblastic leukemia (ALL). Each set of tumors shared a common clonal origin, as demonstrated by expression of identical, unique CDR IIIH sequences, shared somatic mutations in JH, and identical bcl-2 translocation breakpoints of microdissected ALL cells. Molecular analysis of lambda V-gene expression demonstrated lambda-bearing cells in the original kappa tumor, while expansion of the lambda subclone at relapse occurred after active immunotherapy targeting the Ig receptor.

Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma.

The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell-dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody-based chemotherapy of mantle cell lymphoma in first remission.

Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen.

Purpose: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients.

Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes.

The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a tumor-specific antigen and an attractive target for active immunotherapy. While Ab's specific for tumor idiotype have been well described in patients with B cell malignancies, the precise antigenic epitopes in human idiotype recognized by autologous T cells remain largely unknown. We report here that T cell lines generated from lymphoma patients actively immunized with idiotype protein specifically recognized multiple, unique immunodominant epitopes in autologous tumor idiotype.