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

Abstract

Methods Patients , vaccine, and PBMC samples. Patients with advanced FL enrolled on this institutional review board-approved vaccine study were described previously (17). Briefly, patients had received chemotherapy to the first complete remission. Following at least 6 months of immune recovery, they received five subcutaneous injections of autologous, tumor-derived Ig protein conjugated to KLH (Id-KLH), mixed with human recombinant GM-CSF (rGM-CSF). While for FL patients the Id was isolated from heterohybridomas generated by fusion with tumor B cells, for myeloma patients the Id was isolated from patients' serum by affinity chromatography (17). Blood samples were collected from the patients

Vaccine Therapy for B-Cell Lymphomas: Next-Generation Strategies

“…10 Finally, definitive characterization of anti-idiotype cellular immune responses have defined the unique immunodominant peptide epitopes within the hypervariable complementarity-determining regions (CDR), but not framework regions of immunoglobulin heavy chain, recognized by lymphoma-specific T cells. 35 Taken together, these results support the use of lymphoma vaccines in the setting of B-cell depletion induced by rituximab-based induction regimens. However, because the relative role of cellular versus humoral immunity for vaccine efficacy is uncertain, it may be advisable to administer booster vaccinations following B-cell recovery to optimize humoral responses.…”

Dendritic Cell-Based Therapeutic Vaccination against Myeloma: Vaccine Formulation Determines Efficacy against Light Chain Myeloma

“…Although peptides derived from L chain CDRs may express T cell epitopes, anti-Id T cell reactivity is mostly directed against peptides derived from H chain CDRs, especially from the V-D-J (V H -D-J H ) CDR3 region. The predominance of immunity against H chains has been observed in many Id-vaccination studies in multiple myeloma and lymphoma patients (47)(48)(49)(50)(51). This general predominance of Id-specific T cell responses directed against sequences of H chain CDRs, especially CDR3, is attributed to the much larger versatility of H chains, which is mainly determined by their D segment (49).…”

Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials

“…An immune response to unique Ags that was found to be associated to a clinical benefit has been described in patients with renal cancer cells vaccinated with GM-CSF gene-transduced tumor cells (43) and patients with melanoma as indirectly shown from the analysis of clonal T cell response in patients immunized with a (48,49). T cell reactions against multiple unique epitopes were documented and found to be associated with molecular remission in a significant fraction of patients (48).…”

“…How to design clinical trials that preferentially boost the immune response targeting truly tumor-specific unique Ags? While this is relatively easy and already possible for tumors of hematological origin as B cell lymphomas whose altered Ig Id can be sequenced and used as patient-specific unique tumor Ag (48,49), it represents a quite difficult task for solid human tumors. Obviously, the ultimate strategy for targeting such types of Ags will imply sequencing of the whole genome of each individual tumor followed by the selection of mutated peptides whose motifs are predicted to be presented by the HLA alleles of the patient bearing that particular mutated tumor.…”