RT info:eu-repo/semantics/article
T1 Intraclonal Variability of VH Genes in Follicular Lymphoma Patients Who Have Received Anti-Idiotypic Immunotherapy
A1 Barrios del Pino, Yvelise
A1 Yáñez, Rosa
A1 Cabrera, Rafael
A1 Díaz-Espada, Fernando
A2 Medicina InternaDermatología y Psiquiatría
A2 Hospital Puerta de Hierro
K1 non-Hodgkin lymphoma immunotherapy
K1 subclones
K1 lymphoma
K1 idiotypes
K1 tumour vaccines
AB Subclonal heterogeneity can affect idiotypic determinants present in the clonotypic immunoglobulin of B-cell follicularlymphomas (FLs) and may limit the effect of antilymphomatreatments performed by immunization of patients with their owntumor-associated idiotypic immunoglobulin. Idiotype-secreting hybridomas were obtained by fusion of tumor cells from 5 patients withFL, and the K6H6/B5 human heteromyeloma and rearranged VHgenes from tumor samples and hybridomas were amplified, cloned,and sequenced. Sequences were aligned with germline genes andsomatic mutations, intraclonal heterogeneity and genealogic relationsof the B-cell clones in the different biopsy specimens weredetermined. The VH sequence of the progenitor clone was determinedin samples of the tumoral population. Further diversification resulted inthe presence of 2 to 6 subclones in 4 of the 5 samples studied. Only in1 patient did the hypermutation mechanism introduce differencesamong most of the potential idiotopes present in individualsubclones. The VH sequence of the hybridoma that provided theidiotypic-vaccine was identified in one of the tumor subclones in allcases. No relapse has been demonstrated in 3 of the 4 vaccinatedpatients (follow-up: 29–103 months). We conclude that despitepotential differences in the idiotypic region expressed by individualtumor cells, at least some potential idiotopes may be preserved amongall the tumor subclones in most cases studied. All vaccinated patientsdeveloped immune responses against the autologous tumor idiotypicimmunoglobulin. Polyclonal anti-idiotypic immune responses inducedwith a vaccine obtained from 1 hybridoma may be effective against allthe idiotypic variants present in the tumor population.
YR 2006
FD 2006
LK http://riull.ull.es/xmlui/handle/915/34915
UL http://riull.ull.es/xmlui/handle/915/34915
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DS Repositorio institucional de la Universidad de La Laguna
RD 24-nov-2024